Asano, Takeshi; Sudoh, Mariko; Watanabe, Makoto; Fujino, Osamu
Although anemia frequently occurs in poststreptococcal acute glomerulonephritis (PSAGN), severe anemia is rare. We report severe normocytic, normochromic anemia (hematocrit, 19.8%) in PSAGN in a 6-year-old girl with edema, macrohematuria, and proteinuria for 1 month. The potential causes of severe anemia found in this case were: 1) longer duration of massive hematuria from onset of macrohemauria to treatment, 2) a level of erythropoietin much lower than that in cases of iron deficiency anemia, and 3) hemodilution. We speculate that these factors combined to cause an unusual case of severe anemia in PSAGN.
Takashima, Tsuyoshi; Hirata, Sae; Nonaka, Mai; Matsumoto, Keiichiro; Awanami, Yuki; Yamasaki, Masatora; Fukuda, Makoto; Miyazono, Motoaki; Ikeda, Yuji
Retropharyngeal abscess is an infection involving the retropharyngeal space which is posterior to the pharynx and oesophagus, and it results as a complication of a primary infection elsewhere in the head and neck including the nasopharynx, paranasal sinuses, or middle ear, which drain lymph to the retropharyngeal lymph nodes. Their lymph nodes are prominent in children and atrophy with age. Therefore, retropharyngeal abscess is most frequently encountered in children, with 75% of cases occurring before the age of 5 years, and often in the first year of life. We experienced a rare adult case of poststreptococcal acute glomerulonephritis with a retropharyngeal abscess, and conservative therapy ameliorated them. According to past reports, only one child with a retropharyngeal abscess and poststreptococcal acute glomerulonephritis has been presented at a conference to date; this is the first adult case of poststreptococcal acute glomerulonephritis with a retropharyngeal abscess. Retropharyngeal abscess can be fatal including airway compression, so it is important to remember retropharyngeal abscess in a case of poststreptococcal acute glomerulonephritis with severe symptoms of neck.
Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi
We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.
Horita, Yoshio; Tadokoro, Masato; Taura, Koichi; Suyama, Naofumi; Taguchi, Takashi; Miyazaki, Masanobu; Kohno, Shigeru
We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.
Kuniyoshi, Yasutaka; Kamura, Azusa; Yasuda, Sumie; Tashiro, Makoto
Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients.
Cronin, W; Deol, H; Azadegan, A; Lange, K
It is now generally accepted that acute post-streptococcal glomerulonephritis (PSGN) is the consequence of the formation of antigen-antibody-complement complexes on the basement membrane of the glomerulus and that the antigen is of streptococcal origin. In cases of acute PSGN a high titre of specific antibodies to a streptococcal cytoplasmic extract can be found at the very beginning of the disease. This cytoplasmic antigen which we called endostreptosin (ESS) is probably the pathogenetic antigen of glomerulonephritis. It is deposited on the subendothelial side of the basement membrane in the first few days of the disease and is rapidly covered by newly-formed and specific antibody and complement with resultant immune injury causing signs and symptoms of symptomatic but also frequently asymptomatic acute glomerulonephritis. To further characterize and isolate ESS we used immunoaffinity chromatography and Western blotting techniques. PAGE analysis of the affinity-isolated ESS revealed the major component to have a molecular weight of approximately 45 kD. Sera from patients with PSGN or sera of rabbits immunized with affinity-isolated ESS reacted by Western blotting with at least one antigenic component with a molecular weight of approximately 45 kD. Normal human sera or the sera of non-immunized rabbits failed to demonstrate activity against this antigen. The basement membranes of the glomeruli of patients with very early PSGN stain with fluorescein-labelled gammaglobulin of patients with glomerulonephritis. This staining can be prevented when these sera are pre-absorbed with ESS but not by pre-absorption with intact cells or cytoplasmic extracts of other bacteria. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:2667818
Rus, Rina R; Toplak, Nataša; Vizjak, Alenka; Mraz, Jerica; Ferluga, Dušan
There are only a few reports of the co-occurrence of acute poststreptococcal glomerulonephritis (APGN) and acute rheumatic fever. We report an unusual case of a 3-year-old boy with nephrotic syndrome and acute renal failure with the transitional need for peritoneal dialysis, biopsy-proven atypical IgA-dominant APGN, and concomitant acute rheumatic fever, successfully treated by steroids. Aggressive treatment with pulses of methylprednisolone proved to be successful and we recommend its use in this type of cases. PMID:26718763
Hisano, Satoshi; Matsushita, Misao; Fujita, Teizo; Takeshita, Morishige; Iwasaki, Hiroshi
The aim of the present study was to elucidate the correlation between complement pathways and clinicopathological findings in post-streptococcal acute glomerulonephritis (PSAGN). Immunohistological staining was performed on renal specimens obtained from 18 patients with PSAGN and 20 controls, using antibodies against IgG, IgA, IgM, C1q, C3c, C4, fibrinogen, factor B, C4-binding protein (C4-bp), C5b-9, CD59, mannose-binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1). Controls showed no deposition of any antibody. In seven patients, glomerular deposits of C3c, C4, factor B, C4-bp, C5b-9, CD59, MBL and MASP-1 were found. In the remaining 11 patients, glomerular deposits of neither C4 nor MBL/MASP-1 were found, and glomerular deposits of C3c, factor B, C5b-9 and CD59 were evident. C4-bp was detected in seven of these 11 patients. Glomerular deposits of fibrinogen were detected in five of seven patients with MBL/MASP-1 deposits and in only two of 11 patients without MBL/MASP-1 deposits. Hematuria was prolonged in three of seven patients with MBL/MASP-1 deposits through follow up, whereas urinalysis was normal in all patients without MBL/MASP-1 deposits. However, the histological indicators were not different between the two groups. To the authors' knowledge this is the first report to show that complement activation through both the alternative and lectin pathways is evident in some patients with PSAGN. Complement activation is promoted in situ in the glomerulus.
Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H
Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301
Adikari, Madura; Priyangika, Dilani; Marasingha, Indika; Thamotheram, Sharmila; Premawansa, Gayani
Posterior reversible encephalopathy syndrome is a clinical radiographic syndrome of heterogeneous etiologies. Developing hypertensive encephalopathy following post-streptococcal glomerulonephritis is a known but uncommon manifestation and developing posterior reversible encephalopathy syndrome in such a situation is very rare. We report a case with contrast-enhanced computed tomography and magnetic resonance imaging findings of posterior reversible encephalopathy syndrome in the background of acute post-streptococcal glomerulonephritis. A thirteen-year-old Sri Lankan boy presented with a focal fit by way of secondary generalization with duration of 10 minutes, and developed 2 similar fits subsequently following admission. He later developed severe hypertension with evidence of glomerulonephritis, which was diagnosed as acute post-streptococcal glomerulonephritis. A contrast-enhanced computed tomography imaging of brain done on day-3 revealed non-enhancing low-attenuating areas in fronto-parietal regions. A T2 weighted film of magnetic resonance imaging was done on day-10 of the admission and found to have linier sub-cortical hyper intensities in both parietal regions which were compatible with the radiological diagnosis of posterior reversible encephalopathy syndrome. Post-streptococcal glomerulonephritis is an important cause of acute nephritic syndrome especially in children. This case report illustrates a rare association of posterior reversible encephalopathy syndrome in a patient with post-streptococcal glomerulonephritis.
Bottinor, Wendy; Fronk, Daniel; Sadruddin, Salima; Foster, Harriet; Patel, Nilang; Prinz, Andreas; Jovin, Ion S
Pericarditis in conjunction with nephritis is an uncommon clinical scenario with a broad differential diagnosis. We present the case of a 58-year-old male who developed nephritis and pericardial effusion with tamponade physiology. In the following, we discuss the differential diagnosis for concomitant nephritis and pericarditis and discuss the work-up performed on our patient. We also review the epidemiology of postinfectious glomerulonephritis in adults and describe previous cases of Streptococcus pyogenes pericarditis in the literature. PMID:27826373
Bottinor, Wendy; Fronk, Daniel; Sadruddin, Salima; Foster, Harriet; Patel, Nilang; Prinz, Andreas; Jovin, Ion S
Pericarditis in conjunction with nephritis is an uncommon clinical scenario with a broad differential diagnosis. We present the case of a 58-year-old male who developed nephritis and pericardial effusion with tamponade physiology. In the following, we discuss the differential diagnosis for concomitant nephritis and pericarditis and discuss the work-up performed on our patient. We also review the epidemiology of postinfectious glomerulonephritis in adults and describe previous cases of Streptococcus pyogenes pericarditis in the literature.
Marshall, Catherine S.; Cheng, Allen C.; Markey, Peter G.; Towers, Rebecca J.; Richardson, Leisha J.; Fagan, Peter K.; Scott, Lesley; Krause, Vicki L.; Currie, Bart J.
Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0–54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6–94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed. PMID:21976576
Chiu, Chih-Yung; Huang, Yhu-Chering; Wong, Kin-Sun; Hsia, Shao-Hsuan; Lin, Chi-Jen; Lin, Tzou-Yien
Acute poststreptococcal glomerulonephritis(PSGN) is characterized by an abrupt onset of edema,hypertension, and hematuria. Although the association of pulmonary edema with acute glomerulonephritis has been established, it is uncommon for children with PSGN to present with respiratory distress due to pulmonary edema. We encountered six such patients, aged 6-10 years, during a 10-month period. The demographic data, clinical manifestations, laboratory data, radiographic pictures, and clinical courses were collected. All patients presented to the primary pediatricians with dyspnea and alveolar infiltrates with bilateral pleural effusions on plain chest radiographs that were misinterpreted as pneumonia initially. The diagnosis of PSGN was de-layed until the awareness of the presence of pulmonary edema complicating PSGN. Subsequent urinalysis and blood pressure measurement all showed microscopic hematuria and hypertension. Elevated serum antistreptolysin 0 titers and depressed serum complement C3 levels confirmed the diagnosis of PSGN. Two patients progressed to respiratory failure because of a delayed diagnosis of PSGN. All patients recovered without sequelae following appropriate diuresis and antihypertensive therapy. We conclude that in preschool and school-age children who present with dyspneic respirations and a chest radiograph showing radiographic features of pulmonary edema, proper evaluation including blood pressure recording and urinalysis should be performed immediately. Prompt diagnosis and early therapy of PSGNmay avoid mortality and unnecessary therapeutic intervention.
Ulusoy, Sukru; Ozkan, Gulsum; Sonmez, Mehmet; Mungan, Sevdegül; Köseoğlu, Rahman; Cansız, Muammer; Kaynar, Kübra
In addition to being the main cause of glomerulonephritis in children, poststreptococcal glomerulonephritis (PSGN) has recently been shown in older patients, especially those with malignancy or diabetes mellitus. The pathogenesis of PSGN has been ascribed to activation of complement 3 (C3) of the alternative complement cascade which, along with immunoglobulin (Ig) G and IgM deposits, is observed in renal tissue. Our aim here is to discuss the probable causes of PSGN developing with isolated IgM deposition in a 52-year-old patient with essential thrombocytosis followed-up over the previous 3.5 years. These characteristics make our case the first to be reported in the literature.
Sung, Hye-Young; Lim, Chang Hoon; Shin, Mi-Jung; Kim, Young Ok; Song, Ho-Chul; Kim, Suk Young; Choi, Euy Jin; Chang, Yoon Sik; Bang, Byung Kee
Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex ("hump"). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment. PMID:18162726
Kanai, Hiroaki; Sawanobori, Emi; Koizumi, Keiichi; Ohashi, Ryuji; Higashida, Kosuke
Post-streptococcal glomerulonephritis (PSGN) generally has a good renal prognosis, and immunosuppressive therapies are not needed. However, a few patients present with severe acute kidney injury and extensive crescent formations. The etiology of such patients is not well known, and involvement of anti-neutrophil cytoplasmic antibodies is rarely reported. A 9-year-old girl with rapidly progressive nephritic syndrome was diagnosed with PSGN. A biopsy showed diffuse crescentic glomerulonephritis with immunoglobulin G and C3 deposits; moreover, humps were observed on electron microscopy. After she was administered methylprednisolone pulse therapy and intravenous cyclophosphamide, followed by prednisolone and azathioprine therapy, her urinary abnormalities improved and renal function normalized. However, the myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) titers gradually increased. We speculated that PSGN may be augmented by increased MPO-ANCA levels. Therefore, the patient is currently being treated with losartan, enalapril, azathioprine, and prednisolone. Although the MPO-ANCA titer remains high, urinary findings show mild proteinuria and her renal function has been norma for 18 months since onset. A progressive clinical course and severe histological findings may indicate the involvement of ANCA in deterioration of condition in patients with PSGN. Furthermore, in such cases immunosuppressive therapies should be considered even in pediatric PSGN.
Sebastian, Alphy A; Ahsan, Auswaf K
Hutchinson-Gilford progeria syndrome is a rare autosomal dominant disorder associated with skin fragility. It is characterized by craniofacial disproportion, delayed dentition, micrognathia, and plucked bird appearance. The genetic defect is mainly de nova mutation in the lamin A gene. This report describes a 16-year-old patient with classical features of progeria along with post-streptococcal glomerulonephritis. The symptoms of hepatomegaly were also present in the patient. The differential diagnoses of this lesion are also discussed in detail in this literature.
El Said, W; Awad, S; Farid, F; Maged, Z; Fattah, F A; El Maghraby, M
Twenty-one cases of acute glomerulonephritis in children with no previous history of renal disease were studied. Urinary infection with a rising titre of serum agglutinins against the organisms isolated from urine was found in 5 cases. No evidence of previous streptococcal infection was found in these cases. In the meantime all 8 cases with post-streptococcal glomerulonephritis remained without bacteriuria. In one case acute glomerulonephritis followed virus hepatitis, and in the remaining 7 cases the cause of glomerulonephritis was unknown. It is suggested that in predisposed patients the bacteria present in urinary infections might act as antigens starting immunologic reactions in the glomeruli, leading to glomerulonephritis. The final proof of this theory awaits immunofluorescence identification of these antigens in the glomeruli.
Underland, Lisa J; Villeda, Gerson A Vallencia; Pal, Abhijeet; Lam, Leslie
Thyroid storm has a high mortality rate and is often associated with a precipitating factor such as intercurrent illness or infection. It is rare in pediatric patients. Cardiac disease in hyperthyroidism mostly manifests itself as tachycardia but more serious cardiac findings have also been described. A 5-year-old male with recent strep throat infection presented with dilated cardiomyopathy, hematuria, and symptoms and lab findings consistent with severe hyperthyroidism. He was diagnosed with thyroid storm secondary to concurrent Graves' disease and poststreptococcal glomerulonephritis (PSGN). After starting the treatment with methimazole and a beta-blocker, his cardiac disease gradually improved and the PSGN resolved over time. There are no specific pediatric criteria for thyroid storm. Adult criteria can be difficult to apply to pediatric cases. Criteria for diagnosis of thyroid storm are less clear for pediatric patients. Dilated cardiomyopathy is a rare cardiac manifestation of hyperthyroidism. PSGN is due to glomerular immune complexes and can complicate group A strep infection. Providers should be aware of cardiac disease as a complication of hyperthyroidism. PSGN should not mechanistically be related to hyperthyroidism but can precipitate the signs of thyroid storm such as hypertension. This association has not been previously reported in the literature.
... following: Decreased urine output Rust-colored urine Swelling (edema), general swelling, swelling of the abdomen, swelling of ... Exams and Tests A physical examination shows swelling (edema), especially in the face. Abnormal sounds may be ...
Kanodia, Kamal V; Vanikar, Aruna V; Kute, Vivek Balkrishna; Trivedi, Hargovind L
Malaria remains a major health problem in many parts of the world leading to high morbidity and mortality related to renal dysfunction and relapsing nature of Plasmodium vivax malaria. Acute renal failure occurs commonly in Plasmodium falciparum malaria, although its rare occurrences have been reported in P. vivax malaria also. We reported a rare case of P. vivax malaria monoinfection associated with acute post infectious glomerulonephritis.
Vernon, Katherine A.; Goicoechea de Jorge, Elena; Hall, Angela E.; Fremeaux-Bacchi, Veronique; Aitman, Timothy J.; Cook, H. Terence; Hangartner, Robert; Koziell, Ania; Pickering, Matthew C.
Acute poststreptococcal glomerulonephritis is a common cause of acute nephritis in children. Transient hypocomplementemia and complete recovery are typical, with only a minority developing chronic disease. We describe a young girl who developed persistent kidney disease and hypocomplementemia after a streptococcal throat infection. Kidney biopsy 1 year after presentation showed isolated glomerular complement C3 deposition, membranoproliferative changes, and subendothelial, intramembranous and occasional subepithelial electron-dense deposits consistent with C3 glomerulopathy. Complement gene screening revealed a heterozygous single nucleotide insertion in exon 4 of the complement factor H–related protein 5 gene (CFHR5), resulting in a premature stop codon. This variant was not detected in 198 controls. Serum CFHR5 levels were reduced. The mother and sister of the index patient were heterozygous for the sequence variant, with no overt evidence of kidney disease. We speculate that this heterozygous CFHR5 sequence variant is a risk factor for the development of chronic kidney disease after streptococcal infection. PMID:22503529
Shimohata, Homare; Higuchi, Takashi; Ogawa, Yujiro; Fujita, Shogo; Nagai, Miho; Imaizumi, Masahiro; Maruyama, Hiroshi; Hirayama, Kouichi; Kobayashi, Masaki
Human parvovirus B19 (HPV B19) infection is well known as a cause of erythema infectiosum in children. Acute glomerulonephritis due to HPVB19 infection is rarely observed in adults. Here, we present the case of a 45-year-old female who showed acute glomerulonephritis induced by HPVB19 infection with various autoantibodies. She had proteinuria (175 mg/g creatinine) and hematuria (20-29 erythrocytes per high-power field) in a urinalysis, and various autoantibodies such as antinuclear antibodies, proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA), antiglomerular basement membrane (GBM) antibodies, and anticardiolipin antibodies in a blood examination. A renal biopsy showed that endocapillary proliferative glomerulonephritis comprised of mononuclear cell infiltration. By using immunofluorescence microscopy, IgG, IgA, IgM, C3, C4, and C1q deposits were detected mainly in glomerular capillaries. Electron-dense deposits were detected in the subendothelial area and mesangial area by using electron microscopy. All symptoms and abnormal laboratory data were self-improved. Our patient's case may provide a clue to the etiology of ANCA-associated vasculitis or lupus nephritis.
Welch, Thomas R
Acute glomerulonephritis (AGN) is a common condition in childhood. Many children with AGN can be managed in the primary care setting. The diagnosis is usually made on the basis of urinary findings, especially the presence of red blood cell casts. One of the most important initial investigations is determining the complement C3 level; hypocomplementemia is most characteristic of post streptococcal AGN, while normocomplementemia is most often seen with IgA nephropathy. Children whose AGN is accompanied by significant hypertension or renal insufficiency should be assessed by a specialist immediately. The presence of serious extrarenal signs or symptoms also merits urgent referral. Otherwise, serial followup in the primary care office is appropriate.
The influence of birthweight, past poststreptococcal glomerulonephritis and current body mass index on levels of albuminuria in young adults: the multideterminant model of renal disease in a remote Australian Aboriginal population with high rates of renal disease and renal failure.
Hoy, Wendy E; White, Andrew V; Tipiloura, Bernard; Singh, Gurmeet R; Sharma, Suresh; Bloomfield, Hilary; Swanson, Cheryl E; Dowling, Alison; McCredie, David A
Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a 'multihit' model of albuminuria in young adults in one remote Aboriginal community. Urinary albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years and evaluated in the context of birthweights, a history of 'remote' poststreptococcal glomerulonephritis (PSGN; ≥5 years earlier) and current body mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of subjects and 22.8% had a remote history of PSGN. ACR levels rose with age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25% of males and 45% of females). In multivariate models, birthweight (inversely), remote PSGN and current BMI were all independent predictors of ACR levels. The effects of birthweight and PSGN and their combination were expressed through amplification of ACR levels in relation to age and around the group median BMI of 20.8 kg/m(2). In people with BMI <20.8 (57.8% of all males and 40.3% of the females), LBW and PSGN alone had minimal effects on ACR, but in combination they strikingly amplified ACR in relation to age. Those with BMI ≥20.8 (which included 42.2% of the males and 59.7% of the females) had higher ACR levels, and both LBW and a PSGN history, separately and in combination, were associated with striking further amplification of ACR in the context of age. Much of the great excess of disease in this population is explained by high rates of the early life risk factors, LBW and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
O'Donnell, D; Markowitz, S
Acute glomerulonephritis complicated secondary infection in a patient suffering from traumatic blisters caused by new footwear. This unlikely setting for acute glomerulonephritis was made more interesting by its occurrence in an adult in contrast with its more frequent recognition in a child. The age of the patient and the severity of the local symptoms masked the significance of the initial finding of haematuria until deteriorating renal function indicated the diagnosis of concomitant glomerular disease.
Garsen, Marjolein; Benner, Marilen; Dijkman, Henry B; van Kuppevelt, Toin H; Li, Jin-Ping; Rabelink, Ton J; Vlodavsky, Israel; Berden, Jo H M; Rops, Angelique L W M M; Elkin, Michael; van der Vlag, Johan
Heparanase, a heparan sulfate (HS)--specific endoglucuronidase, mediates the onset of proteinuria and renal damage during experimental diabetic nephropathy. Glomerular heparanase expression is increased in most proteinuric diseases. Herein, we evaluated the role of heparanase in two models of experimental glomerulonephritis, being anti-glomerular basement membrane and lipopolysaccharide-induced glomerulonephritis, in wild-type and heparanase-deficient mice. Induction of experimental glomerulonephritis led to an increased heparanase expression in wild-type mice, which was associated with a decreased glomerular expression of a highly sulfated HS domain, and albuminuria. Albuminuria was reduced in the heparanase-deficient mice in both models of experimental glomerulonephritis, which was accompanied by a better renal function and less renal damage. Notably, glomerular HS expression was preserved in the heparanase-deficient mice. Glomerular leukocyte and macrophage influx was reduced in the heparanase-deficient mice, which was accompanied by a reduced expression of both types 1 and 2 helper T-cell cytokines. In vitro, tumor necrosis factor-α and lipopolysaccharide directly induced heparanase expression and increased transendothelial albumin passage. Our study shows that heparanase contributes to proteinuria and renal damage in experimental glomerulonephritis by decreasing glomerular HS expression, enhancing renal leukocyte and macrophage influx, and affecting the local cytokine milieu. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng
Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989
Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng
Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450
Nagy, J; Brasch, H; Süle, T; Hámori, A; Deák, G; Ambrus, M
Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.
Jardim, H M; Leake, J; Risdon, R A; Barratt, T M; Dillon, M J
Data on patients with crescentic glomerulonephritis (greater than 50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7-15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR less than 30 ml/min per 1.73 m2) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%-79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m2. In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P less than 0.05). Outcome was not, however, related to the percentage of glomeruli affected (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
López-Gómez, Juan M.; Rivera, Francisco
Background and objectives: Renal biopsy in acute renal failure of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. This study analyzed the frequency and clinicopathologic correlations of renal native biopsied acute renal failure in Spain during the period 1994 through 2006. Design, setting, participants, & measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly. Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group. Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure. PMID:18354075
Helal, Imed; Kaaroud, Hayet; Goucha, Rym; Ben Moussa, Fatma; Ben Maiz, Hedi; Kheder, Adel
Acute post-infectious glomerulonephritis (APIGN) is uncommon in adults. It is widely recognized that the prognosis of APIGN is good in children. There is however little information about its long-term prognosis in adults. Between December 1976 and October 2004, 148 adult cases of APIGN were managed in our center. We retrospectively reviewed these patients' records and evaluated their clinical course and outcome. The mean age of studied patients was 36 ± 15 years, and the male to female ratio was 2.3. The most common site of preceding infection was the respiratory tract (68.8%). At presentation, 89.2% had nephritic syndrome and 9.4% had rapidly progressive glomerulonephritis. Proteinuria was observed in 99.3%, hematuria in 95.3%, peripheral edema in 89.2% and hypertension in 81.8%. Most patients (60.7%) had acute kidney injury and four patients (2.7%) required dialysis. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis in 88.8% of patients, associated with extracapillary proliferation in 12%. After a median follow-up of 2.5 year, only two patients died and 16.12% of patients had persistent clinical and/or biological abnormality. Chronic kidney disease was noted in 10 patients (6.75%) including four patients (2.7%) who progressed to end-stage renal disease. Poor prognostic factors included nephrotic range proteinuria, extracapillary proliferation in renal biopsy, acute kidney injury and the need for dialysis. In this cohort of patients, APIGN progressed to chronic kidney disease in less than 10% of patients.
Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan
The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.
Zheng, Ming-huan; Jiao, Zhen-quan; Zhang, Li-jie; Yu, Sang-jie; Tang, Guang-peng; Yan, Xiao-mei; He, Li-hua; Meng, Fan-liang; Zhao, Fei; Zhang, Mao-jun; Xiao, Di; Yang, Yong-hong; Nie, Wei; Zhang, Jian-zhong; Wang, Zi-jun
In this study, 68 group A streptococcus (GAS) isolates associated with two outbreaks of acute glomerulonephritis (AGN) in China were analyzed by emm typing. A total of 11 different emm types were identified. Analysis of emm type distribution suggested that AGN outbreaks in two counties were caused by emm60.1- and emm63.0-type GAS. These two types were further characterized by pulsed-field gel electrophoresis, multilocus sequence typing, sof sequence typing, and PCR-based identification of streptococcal pyrogenic exotoxin A, B, and C (speA, speB, and speC) genes. In antimicrobial susceptibility tests, all outbreak strains were resistant to erythromycin and tetracycline, and the rates of resistance of nonoutbreak strains to the two antibiotics were 63.6% and 90.9%. This study is also the first to report a nephritogenic M63 GAS strain. PMID:19116348
Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine
Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206
Salter, Tracey; Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine; Hilton, Rachel
Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a "full house" immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting "past resolved" infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.
Pathak, Himanshu; Marshall, Tarnya
A 35-year-old man presented with polyarthritis and constitutional symptoms, and a recent history of multiple tick bites and skin rash on trekking holiday. He did not respond to oral doxycycline and cephalexine for presumed Lyme's disease. Further investigation confirmed strongly positive streptococcal serology. There was absence of clinical or echocardiography evidence of heart involvement and immunological screening for inflammatory arthritis was negative. In the absence of other major Jones criteria for acute rheumatic fever, besides polyarthritis and the serological evidence of a recent streptococcal infection, a diagnosis of post-streptococcal reactive arthritis (PSRA) was also made. He responded well to penicillin therapy and has been started on oral penicillin prophylaxis as per available guidance. As streptococcal infections in the adult population are increasingly reported, it is a timely opportunity to revisit PSRA, and develop comprehensive treatment and antibiotic prophylaxis guidelines. PMID:27520996
Stratta, Piero; Musetti, Claudio; Barreca, Antonella; Mazzucco, Gianna
The association between acute renal disease and infection has been known since the mid '800s: acute post-infectious glomerulonephritis (PIGN) is a reactive immunological process against the kidney secondary to an infection, classically caused by a Streptococcus. The typical clinical presentation of PIGN is an acute nephritic syndrome with macro- or microscopic hematuria, proteinuria, hypertension, edema and renal function impairment of variable degree. The histology is characterized by an intracapillary glomerular proliferation, but may rarely be associated with an extracapillary proliferation. The classical childhood form is still present nowadays, even with severe cases, in developing countries, while in the last decades it almost disappeared in industrialized countries, where post-infectious GN are often found in elderly patients with multiple comorbidities. These clinical variants are usually related to other infective agents, like Staphylococcus aureus, both methicillin resistant (MRSA) and susceptible, and may be characterized by an IgA-dominant deposition. Kidney biopsy is rarely needed, especially in the child, while in the adult or old patient a biopsy is warranted if there is an atypical presentation or evolution, like rapidly progressive renal failure, absent or delayed function recovery, persisting low C3, nephrotic range proteinuria and persisting high proteinuria. Current therapy strategies rely on culture-guided systemic antibiotics, especially in the old patient, in which MRSA are relatively frequent, support therapy and only in very selected cases on steroids. These latter cases include the rare PIGN with crescents and those with a severe interstitial inflammation.
Meyer, P; Soëte, S; Raynaud, P; Henry, V; Morin, D; Rodière, M; Rivier, F; Roubertie, A
Acute inflammatory polyradiculoneuropathy, or Guillain-Barré syndrome (GBS), is characterized by peripheral nerve demyelination, which leads to rapidly progressive weakness, loss of sensation, and loss of deep tendon reflexes. It is a prototype of postinfectious autoimmune disease, whose pathophysiology is well described in the forms provoked by certain bacteria (molecular mimicry with Campylobacter jejuni), but remains unclear for the forms related to other organisms (cytomegalovirus, Epstein-Barr virus and other herpes group viruses, Mycoplasma pneumoniae). Glomerular lesions can be associated with the neurological symptoms and have also been described after various infections, independently of any signs of polyradiculoneuropathy. We report the observation of a 12-year-old girl who presented with Guillain-Barré syndrome with facial diplegia, ataxia, and intracranial hypertension following Epstein-Barr virus (EBV) primary infection. During the course of the neurological disease, membranous glomerulonephritis (MGN) was diagnosed. The neurological impairment was regressive within 6 months after intravenous immunoglobulin treatment followed by intravenous then oral corticosteroid administration. Viremia remained high more than 6 months after the onset of symptoms. Glomerulopathy progressed independently and finally required immunosuppressant medication with cyclosporine. EBV might be the factor that triggered the autoimmune disorders, as previously reported for systemic lupus erythematosus and multiple sclerosis in children. To the best of our knowledge, this association of 3 conditions (GBS, MGN, and EBV primary infection) has never been reported in the literature. Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Seggie, J; Davies, P G; Ninin, D; Henry, J
Ninety-eight Zimbabweans with glomerulonephritis characterised by nephrotic proteinuria were studied. There was no evidence to implicate Schistosoma mansoni or S. haemotobium in the aetiology, although schistosomiasis was diagnosed in 54 patients in the series. Similarly, Plasmodium malariae proved unimportant as a cause of the nephrotic syndrome, only one patient showing focal segmental glomerulosclerosis which was associated with subclinical quartan malarial infection. Nevertheless, infections were shown to play a major role in the genesis of glomerulonephritis which was associated with beta-haemolytic streptococcal, hepatitis B and syphilitic infection in 45 patients in the series. The major patterns of disease in childhood proved to be membranous glomerulopathy associated with hepatitis B antigenaemia. In young adults post-streptococcal proliferative glomerulonephritis constituted the commonest disease pattern. In older adult patients a miscellany of primary and secondary glomerulonephritides was encountered but proliferative glomerulonephritis, which was both idiopathic and streptococcus-related, predominated.
Daga, Mradul Kumar
Ruptured Sinus of Valsalva (RSOV) is a rarely seen disease condition. RSOV can have varied presentations from being asymptomatic with just a cardiac murmur to profound hypotension. There has been simultaneous occurrence of RSOV with Infective Endocarditis (IE) in literature. Glomerulonephritis has also been reported in approximately 20% patients with IE. Large amount of proteinuria or decline in kidney functions is rarely encountered and mostly this finding has been incidental on routine evaluation. The co-existence of all the three conditions in a single patient is rare. This case was diagnosed to have RSOV with IE and was also diagnosed with post-infectious glomerulonephritis on renal biopsy. Patient was advised corrective cardiac surgery, but due to financial constraints, patient could not be operated and he died. Here, we report for the first time an unusual presence of both RSOV and sub-aortic membrane with IE complicated by glomerulonephritis. PMID:27891383
Mori, Y; Yamashita, H; Umeda, Y; Uchiyama-Tanaka, Y; Nose, A; Kishimoto, N; Kijima, Y; Nagata, T; Mori, M; Matsubara, H; Yoshida, H; Iwasaka, T
An otherwise healthy 20-year-old woman presented with an erythematous rash on her face as well as arthralgia and anemia. She also had systemic edema, proteinuria and hypertension. Laboratory data on admission showed hypocomplementemia, human parvovirus B 19 (HPV) DNA and both immunoglobulin (Ig) M and IgG antibodies to HPV in her serum. Renal biopsy specimens showed features of endocapillary glomerulonephritis under light microscopy. Electron microscopy showed massive subendothelial electron-dense deposits. No cause was probable other than immune complex-mediated glomerulonephritis associated with HPV infection. In a review of this and similar cases reported in the literature, several characteristic features come to light: female dominance, onset in the second or third decade of life, hypocomplementemia, histologic renal endocapillary and/or mesangioproliferative glomerulonephritis with subendothelial deposits and spontaneous recovery.
Krishnamurthy, Sriram; Choudhary, Bharat; Rajesh, Nachiappa Ganesh; Ramesh, Ananthakrishnan; Srinivasan, Sadagopan
An 11-year-old girl with clinical features of Kartagener syndrome presented with signs of acute glomerulonephritis. Blood urea and creatinine were mildly elevated and anti-streptolysin O and C3 levels were normal. Renal biopsy demonstrated mesangial proliferation and direct immunofluorescence showed IgM and C3 deposits. This appears to be the first report of Kartagener syndrome in association with mesangioproliferative glomerulonephritis. The literature is reviewed and the possible mechanisms for this association are discussed.
Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222
... salt, and potassium diuretics (medicines that increase urine production) medicines to lower blood pressure (if high blood pressure is a problem) antibiotics (if a bacterial infection is causing glomerulonephritis) steroids ...
Enríquez, Ricardo; Sirvent, Ana Esther; Amorós, Francisco; Pérez, Miguel; Matarredona, Jaime; Reyes, Adolfo
We describe the association of crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome. A 39-year-old woman presented edema and proteinuria and later a non-pruritic urticarial rash. Laboratory results showed nephrotic syndrome, hypocomplementemia and positive anti-C1q antibodies. Skin biopsy disclosed leukocytoclastic vasculitis. Acute renal failure developed. Renal biopsy revealed crescentic membranoproliferative glomerulonephritis. She was treated with corticosteroids and cyclosphosphamide with improvement of the renal function and partial remission of the nephrotic syndrome. Afterwards the nephrotic syndrome relapsed, mycophenolate mofetil in monotherapy was administered with reduction in proteinuria. As far as we know only 3 cases, 2 in children and one in an adult, of crescentic glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome have been reported. In our patient renal manifestations preceded urticarial lesions. We provide information on the evolution during a 42-month follow-up.
Shah, H. H.; Thakkar, J.; Pullman, J. M.; Mathew, A. T.
Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that commonly presents clinically with hypertension, proteinuria, microscopic hematuria, and varying degree of renal insufficiency. Histologically, FGN can present with different patterns of glomerular injury, more commonly mesangioproliferative, membranoproliferative, and membranous nephropathy. While crescent formation has been described in some kidney biopsy series of FGN, crescentic glomerulonephritis pattern of glomerular injury has been rarely described. Optimal therapy and outcomes in FGN presenting with crescentic GN is not currently known. We report an adult patient who presented with massive proteinuria and severe renal failure. The kidney biopsy revealed crescentic FGN (C-FGN). The patient remained dialysis dependent despite immunosuppressive therapy. We also briefly review FGN, and the few reported cases of C-FGN that presented as rapidly progressive or advanced renal failure in the literature. PMID:28356674
Elfenbein, I B; Baluarte, H J; Cubillos-Rojas, M; Gruskin, A B; Coté, M; Cornfeld, D
Histologic patterns in the glomerular tufts in "Glomerulonephritis with many crescents" take three main forms: (1) compression and sclerosis of glomeruli, (2) necrotizing glomerulitis, and (3) proliferation with or without exudation. In the third group, histologic differentiation between patients with poststreptococcal glomerulonephritis with many crescents (AGN) and those with nonstreptococcal rapidly progressive glomerulonephritis (RPGN) may be impossible. In a retrospective study, quantitative morphometry of glomeruli effectively separated three patients with AGN from two patients with RPGN after the usual histologic and electron microscopic observations had failed. Parameters studied were areas of tufts and crescents and total number of cells and granulocytes in tufts and crescents. Surface areas of tufts and crescents were separately determined by photographing glomeruli, projecting and tracing outlines of tufts and crescents, and cutting out and weighing the tracings. The cell density of glomerular tufts (cell per 1000-sq. mum. area) was significantly greater in AGN than in RPGN when either total cell densities (17.64 plus or minus 0.41 versus 13.63 plus or minus 0.30) or total cells minus granulocytes (16.39 plus or minus 0.50 versus 12.99 plus or minus 0.52) were compared. The cell density in the tufts was 120 and 70 per cent greater than controls in AGN and RPGN, respectively. Exudation of inflammatory cells is contributory but not the major cause of hypercellularity in AGN. Follow-up studies with biopsies showed marked resolution in two of three patients with AGN, with normal blood urea nitrogen levels and focal scarring in the third, whereas the two patients with RPGN had either extensive scarring and reduced renal function or required chronic hemodialysis.
Papa, Riccardo; Consolaro, Alessandro; Minoia, Francesca; Caorsi, Roberta; Magnano, Gianmichele; Gattorno, Marco; Ravelli, Angelo; Picco, Paolo
In 1966, Goldbloom et al. described two children who developed a peculiar clinical picture characterized by intermittent daily bone pain in the lower limbs, fever spikes, increased acute phase reactants and dysproteinaemia. The syndrome occurred two weeks after a group A β-haemolytic streptococcus infection. So far, only a few cases have been reported in the medical literature in English. We report two further cases of Goldbloom's syndrome with a review of the literature in English. Our two patients lived in the same Italian region and presented their syndrome onset a week apart. Early use of STIR MRI revealed an atypical metaphyseal hyperintensity in the femurs and tibias. X-ray showed periosteal hyperostosis. A short cycle of corticosteroids led to rapid recovery of symptoms and disappearance of bone changes. The reported cases highlight a likely under-recognised post-streptococcal inflammatory periosteal reaction and emphasise the diagnostic utility of the newer imaging modalities.
Anjos, Lais Martins Moreira; Marcondes, Mariana Barros; Lima, Mariana Ferreira; Mondelli, Alessandro Lia; Okoshi, Marina Politi
Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.
Suehiro, T; Masutani, K; Yokoyama, M; Tokumoto, M; Tsuruya, K; Fukuda, K; Kanai, H; Katafuchi, R; Nagatoshi, Y; Hirakata, H
A 15-year-old boy developed nephrotic syndrome and acute renal failure 4 years after allogenic bone marrow transplantation (BMT) for lymphoid crisis of chronic myelocytic leukemia. On admission, he presented with clinical features of chronic GVHD including transient exacerbation of cholestatic liver injury. Renal biopsy showed diffuse proliferative glomerulonephritis with cellular crescents. The patient was treated with methylprednisolone pulse therapy (1 g/day, for 3 days) followed by oral prednisolone. Renal function gradually improved but nephrotic state was persistent. A second renal biopsy showed improvement of acute tubular necrosis and endocapillary proliferation and transformation of crescents into a fibrous form. After tapering of oral prednisolone, cyclophosphamide was started, which resulted in a gradual improvement of proteinuria. Several cases of nephrotic syndrome occurring after BMT have already been reported, but most cases had membranous nephropathy. In our case, renal biopsy revealed diffuse proliferative glomerulonephritis with findings of active cellular immunity, and aggressive treatment resulted in attenuation of these findings. Moreover, chronic GVHD-related liver injury was noted at the time of this episode. Our findings suggest that chronic GVHD may be complicated with diffuse proliferative glomerulonephritis through unknown cellular immune mechanism.
Mágori, A; Sonkodi, S; Lászik, Z; Mohácsi, G
Diagnosis of glomerulonephritis (GN) is rare among diabetics and few data relevant to this issue can be found in literature. In Institute of Pathology of "Szent-Györgyi Albert" University of Medicine the presence of GN was found in cases during the examination of renal biopsy material of 36 diabetics. All patients have suffered from diabetes mellitus of 2nd type and of less than 10 year existence, requiring no insulin treatment. In 2 cases diffuse diabetic glomerulosclerosis associated with GN. It is emphasized that kidney biopsy and its complex--light and electronmicroscopic and immunhistological--examination are essential to the diagnosis of GN of diabetics.
Li, Jun; Liu, Chang-Hua; Xu, Dao-Liang; Gao, Bo
CD163, a marker of M2 macrophages, possesses anti-inflammatory properties. This study aims to investigate the clinicopathological significance of CD163-positive macrophages in proliferative glomerulonephritis. Renal tissue samples from patients with lupus nephritis (LN, n = 22), antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune necrotizing glomerulonephritis (PNGN, n = 10), type 1 membranoproliferative glomerulonephritis (n = 5), minimal change disease (n = 8) and normal control kidneys (n = 3) were included in this study. The expression of CD163, CD68, CD20 and CD3 in renal tissues was detected by immunohistochemistry or immunofluorescence. The level of urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined by enzyme-linked immunosorbent assay. CD163 was mainly expressed in active crescentic glomerulonephritis, proliferative glomerular lesions and areas of tubulointerstitial injury. Patients with LN-IV and PNGN had numerous CD163-positive cells in glomerular and acute tubulointerstitial lesions. CD163-positive cells in glomeruli positively correlated to proteinuria yet negatively correlated to estimated glomerular filtration rate. There was a positive correlation between the number of CD163 cells in acute tubulointerstitial lesions and NGAL levels, whereas a negative correlation between CD163 numbers and estimated glomerular filtration rate. The number of CD163-positive cells in crescentic glomerulonephritis was more than other groups. In LN, the number of CD163 cells in the tubulointerstitial and glomerular lesions had a positive correlation with activity index. Dual staining showed that CD163-positive cells also expressed CD68, although they did not show any staining for CD20 or CD3. CD163-positive macrophages were involved in the pathogenesis of proliferative glomerular lesions, active crescentic glomerulonephritis and acute tubular injury of patients with PNGN and active LN.
Solak, Yalcin; Gaipov, Abduzhappar; Anil, Melih; Atalay, Huseyin; Ozbek, Orhan; Turkmen, Kultigin; Polat, Ilker; Turk, Suleyman
Rapidly progressive glomerulonephritis caused mycobacterium tuberculosis is rare; however, three case have been reported to date. Crescentic glomerulonephritis is a life-threatening disease and together with the presence of tuberculous infection is associated with a poor outcome if treatment is inadequate and delayed. We describe the case of a 31-year-old female patient with nephrotic syndrome and progressive renal failure secondary to pulmonary tuberculosis. Renal biopsy showed crescent formation in 14 out of 27 glomeruli, and there was diffuse linear staining of immunoglobulin G deposits. Treatment included corticosteroids in combination with antituberculosis drugs for 2 months, and resulted in a significant improvement in renal function, the disappearance of proteinuria and pulmonary symptoms. We also present a review of the pertinent literature and discuss the pathophysiology of tuberculosis-related acute postinfectious glomerulonephritis. Copyright © 2012. Published by Elsevier B.V.
Aran, Adi; Weiner, Karin; Lin, Ling; Finn, Laurel Ann; Greco, Mary Ann; Peppard, Paul; Young, Terry; Ofran, Yanay; Mignot, Emmanuel
Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (ASLO) or anti-DNAse B (ADB)]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI), an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61) and PDI (P328-338). The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001). Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001), and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039) and insulin resistance (Homeostatic Model Assessment (HOMA) 4.1 vs. 3.1, n = 1215, p = 0.004), in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances. PMID:20886095
Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302
Ignatenko, G A; Mukhin, I V
Renal lesion deteriorates the course and prognosis of gouty glomerulonephritis. Current pathogenetic therapy is not sufficiently effective. Effects of different treatments on morphological and functional manifestations of renal disorders in experimental gouty glomerulonephritis are reviewed.
Murphy, B F; Gonzales, M F; Ebeling, P; Fairley, K F; Kincaid-Smith, P
Two cases of idiopathic membranous glomerulonephritis associated with acute inflammatory demyelinating polyradiculoneuropathy (Landry-Guillian-Barre syndrome) are described. In both of the patients, the onset of the nephrotic syndrome coincided with the development of severe ascending sensorimotor neuropathy. Although this association has previously been reported in four other isolated cases, it is not generally recognized by nephrologists and may be of significance in the future understanding of the immunopathogenesis of both diseases.
Patel, Mohan P; Kute, Vivek B; Gumber, Manoj R; Gera, Dinesh N; Shah, Pankaj R; Patel, Himanshu V; Trivedi, Hargovind L; Vanikar, Aruna V
Plasmodium vivax infection is increasingly a major public health burden and the second most frequent human malaria. Higher levels of clinical severity and chloroquine resistance are major factors responsible for such increases. Malarial glomerular injury is uncommon and mainly observed in Plasmodium malariae-infected patients. Occasionally, transient immune complex-mediated glomerulonephritis is associated with Plasmodium falciparum infection. Coexistent crescentic glomerulonephritis and vivax malaria have not previously been reported. We report a fatal case of P. vivax malaria, who presented with acute renal failure. P. vivax monoinfection status was diagnosed with peripheral blood smear and rapid antigen test. Further evaluation for renal failure related to systemic illness and immunological markers were inconclusive. He was treated with antimalarial drugs, hemodialysis, and supportive therapy. Renal biopsy performed for nonrecovering renal failure reveled crescentic glomerulonephritis. This case highlights the need to thoroughly search for malaria-associated crescentic glomerulonephritis using renal biopsy after nonrecovering renal failure.
Ismail, Ibrahim; Nigam, Sonu; Parnham, Alan; Srinivasa, Vinay
We report a previously unrecognized and unreported case of a patient with anti-glomerular basement membrane glomerulonephritis following nintedanib, an orally active small molecule tyrosine kinase inhibitor. A 59-year-old Caucasian woman with a history of idiopathic pulmonary fibrosis presented with severe acute kidney injury (creatinine 285 umol/L) secondary to anti-glomerular basement membrane glomerulonephritis disease 4 months after commencement of nintedanib. She had hematuria with red blood cell casts, nephrotic range proteinuria (3.5g/24 hours) and significantly elevated anti-glomerular basement membrane glomerulonephritis titers at 860 chemiluminescent units. A kidney biopsy confirmed severe crescentic glomerulonephritis with linear immunoglobulin G deposition in glomerular basement membrane. Despite the commencement of treatment with plasma exchange and cyclophosphamide, she remained dialysis dependent. Nintedanib was discontinued. Onset of acute anti-glomerular basement membrane glomerulonephritis was found to be associated with recent nintedanib use suggesting that nintedanib may be a potential trigger for anti-glomerular basement membrane glomerulonephritis. This case highlights the importance of close monitoring of patients receiving new targeted therapies. Management of novel targeted agents in patients receiving dialysis is challenging because of the scarcity of specific data.
Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel
Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria’s overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome. PMID:26818712
Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel
Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.
Takeuchi, K; Takeda, T; Sakai, I; Taneichi, K; Shibaki, H
Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.
... seen, including: Nerve inflammation (polyneuropathy) Signs of fluid overload, including abnormal heart and lung sounds Swelling ( edema ) ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...
... of removing extra fluids and waste from your blood — typically by an artificial kidney machine. Chronic kidney disease. Your kidneys gradually lose their filtering ability. Kidney function that deteriorates to less than 10 percent of ... High blood pressure. Damage to your kidneys and the resulting ...
Radis, C D; Callis, K P
This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.
Ram, Rapur; Sandeep, Peddi; Sridhar, Annapindi Venkatasatya Surya Naga; Rukumangadha, Nandyala; Sivakumar, Vishnubotla
The reports of glomerular lesions of kidney due to tuberculosis are sparse. A 48-year-old gentleman, presented with swelling of feet of 3 months duration. As he had renal impairment, proteinuria and normal-sized kidneys, he was subjected to renal biopsy. The light microscopy and immunofluorescence revealed the diagnosis was membrano-proliferative glomerulonephritis. During hospital stay, the patient complained fever and stiffness at thoracic spine. The MRI of thoraco-lumbo-sacral spine revealed paravertebral abscess at D11-D12. The pus aspirated was positive for Mycobacterium tuberculosis. He was started on anti-tuberculous medication. After 8 weeks of therapy, the serum creatinine was 1.5 mg/dL and 24 h urine protein 250 mg.
Miadonna, A; Salmaso, C; Palazzi, P; Elli, A; Braidotti, P; Lambertenghi Deliliers, G
Castleman's disease is an uncommon lymph node disorder which can be associated with renal disease. In this report we describe a patient with fever, weight loss, anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome. Castleman's disease, plasma cell type, was diagnosed by histologic analysis after surgical excision of a pelvic lymph node. The disease was considered localized, since further investigations did not show any other pathologic mass. After resection of the pelvic lymphoid mass, clinical remission of systemic symptoms and laboratory abnormalities was observed, with the exception of the nephrotic syndrome. Renal biopsy was performed and showed a pattern compatible with fibrillary glomerulonephritis. Progressive decline in renal function was observed, despite immunosuppressive therapy.
While antineutrophil cytoplasmic antibody (ANCA) positivity has been documented in some patients with postinfectious glomerulonephritis (PIGN) and is associated with more severe disease, antiphospholipid antibodies (APA) are not known to be a common occurrence. We describe a child with severe acute kidney injury who was noted to have prolonged positivity of both ANCA and APA; a renal biopsy showed noncrescentic immune complex mediated glomerulonephritis with subepithelial deposits compatible with PIGN. He recovered without maintenance immunosuppressive therapy and at last follow-up had normal renal function. We discuss the cooccurrence and implications of ANCA and APA in children with PIGN. PMID:28255306
Peila, Elena; Mortara, Paolo; Cicerale, Alessandro; Pinessi, Lorenzo
We report a case of a 15-year-old boy presenting with sudden attacks of hyperkinetic movements of the limbs, trunk and neck. Clinical features were suggestive of paroxysmal non-kinesigenic dyskinesia, but the elevated antistreptolysin O antibody titre and history of recurrent upper airways infection led us to consider a post-streptococcal syndrome as a possible diagnosis. The patient started therapy with benzathine penicillin, sodium valproate and clonazepam without any significant improvement. A successive psychiatric assessment revealed the presence of a psychogenic movement disorder. Psychodynamic psychotherapy and individual counselling were started with progressive improvement of psychological symptoms and gradual resolution of hyperkinetic episodes, without any recurrence recorded during the follow-up (10 months). PMID:25795754
Peila, Elena; Mortara, Paolo; Cicerale, Alessandro; Pinessi, Lorenzo
We report a case of a 15-year-old boy presenting with sudden attacks of hyperkinetic movements of the limbs, trunk and neck. Clinical features were suggestive of paroxysmal non-kinesigenic dyskinesia, but the elevated antistreptolysin O antibody titre and history of recurrent upper airways infection led us to consider a post-streptococcal syndrome as a possible diagnosis. The patient started therapy with benzathine penicillin, sodium valproate and clonazepam without any significant improvement. A successive psychiatric assessment revealed the presence of a psychogenic movement disorder. Psychodynamic psychotherapy and individual counselling were started with progressive improvement of psychological symptoms and gradual resolution of hyperkinetic episodes, without any recurrence recorded during the follow-up (10 months).
Lung, J M; Mallory, S B
coagulase negative staphylococci in the blood culture were considered to be a contaminant. Cefotaxime and oxacillin were given intravenously. His leg was elevated and cooled with ice packs. The patient's fever resolved within 24 h. The lesion became less erythematous and nontender with decreased warmth and lymphadenopathy. The child was discharged on Duricef for 10 days. Because the patient experienced hematuria rather than hemoglobinuria, nephritis was suggested. In this case, poststreptococcal glomerulonephritis was the most likely cause. His anti-streptolysin-O titer was elevated at 400 U (normal, <200 U) and C3 was 21.4 mg/dL (normal, 83-177 mg/dL). His urine lightened to yellow-brown in color. His blood pressure was normal. Renal ultrasound showed severe left hydronephrosis with cortical atrophy, probably secondary to chronic/congenital ureteropelvic junction obstruction. His right kidney was normal.
Raybould, Jillian E.; Raybould, Alison L.; Morales, Megan K.; Zaheer, Misbah; Lipkowitz, Michael S.; Timpone, Joseph G.; Kumar, Princy N.
Abstract Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis–associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti–neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone. PMID:27885316
Watson, Gabriella; Jallow, Bintou; Le Doare, Kirsty; Pushparajah, Kuberan; Anderson, Suzanne T
Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.
Reich, Heather N.; Tritchler, David; Cattran, Daniel C.; Eichinger, Felix; Boucherot, Anissa; Henger, Anna; Berthier, Celine C.; Nair, Viji; Cohen, Clemens D.
Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. PMID:20976140
Ryffel, B.; Car, B. D.; Gunn, H.; Roman, D.; Hiestand, P.; Mihatsch, M. J.
The ability of interleukin-6 (IL-6) to modulate immune parameters and mesangial cell function suggests a role for this cytokine in the development of autoimmune glomerulonephritis. This hypothesis was tested in 6-month-old female (NZB x NZW)F1 mice that were administered recombinant human IL-6 (rhIL-6) (50 and 250 micrograms/kg s.c.) for 12 weeks, resulting in an accelerated and severe form of membranoproliferative glomerulonephritis associated with marked upregulation of mesangial major histocompatibility complex class II antigen and glomerular ICAM-1 expression. To distinguish direct effects of rhIL-6 on the renal mesangium from those mediated through the immune system, (NZB x NZW)F1 mice were immunosuppressed with cyclosporin. Immunosuppression by cyclosporin inhibited the development of glomerulonephritis, decreased class II antigen expression, and abrogated IL-6-mediated effects. Administration of neutralizing anti-IL-6 antibody had no effect on the spontaneous development of glomerulonephritis in (NZB x NZW)F1 mice. This finding, together with undetectable IL-6 serum levels, makes a pathogenetic role of endogenously produced IL-6 in this disease model unlikely. In contrast to (NZB x NZW)F1 mice, parental NZW or BALB/c mice given high doses of rhIL-6 (500 micrograms/kg) or recombinant murine IL-6 (100 micrograms/kg) daily for 4 weeks failed to develop morphological or biochemical evidence of glomerulonephritis. Induction of acute phase proteins, anemia, thrombocytosis, and induction of renal class II antigen confirmed the biological activity of IL-6 in these mice. In conclusion, while non-nephritogenic in normal mice, IL-6 accelerates the development of the genetically determined glomerulonephritis of (NZB x NZW)F1 mice through effects mediated by a modulated immune system. Since neutralizing IL-6 antibody treatment did not prevent the development of glomerulonephritis, it is unlikely that increased IL-6 production plays a role in the pathogenesis of lupus
Sethi, Sanjeev; Rajkumar, S Vincent
Monoclonal gammopathy is characterized by circulating monoclonal immunoglobulin owing to clonal proliferation of immunoglobulin-producing B lymphocytes or plasma cells. Clonal proliferation of B lymphocytes is seen in B-cell lymphoma/leukemia, and clonal plasma cell proliferation is seen in multiple myeloma and monoclonal gammopathy of undetermined significance. The monoclonal immunoglobulin in the setting of a B-cell or plasma cell disorder can cause a proliferative glomerulonephritis via 2 mechanisms: (1) glomerular deposition of the monoclonal immunoglobulin with activation of the classical pathway of complement (direct mechanism), resulting in an immunoglobulin-positive C3-positive glomerulonephritis, and (2) glomerular deposition of complement factors of the alternative and terminal pathway via inhibition of alternative pathway-regulating proteins by the monoclonal immunoglobulin (indirect mechanism), resulting in immunoglobulin-negative C3-positive glomerulonephritis (C3 glomerulopathy). Evaluation should include serum and urine electrophoresis and immunofixation as well as serum-free light-chain assay. If a monoclonal immunoglobulin is detected on these tests, bone marrow biopsy or imaging is needed to exclude more advanced plasma cell dyscrasia. Evaluation of alternative pathway of complement should be done in patients with Ig-negative C3-positive glomerulonephritis. If monoclonal gammopathy is due to an underlying malignant disease such as myeloma, lymphoma, or chronic lymphocytic leukemia, then specific treatment should be aimed at treating the malignant disease, with the goal of eradicating the clonal cells producing the immunoglobulin. In contrast, if monoclonal gammopathy is due to a monoclonal gammopathy of undetermined significance, treatment options include bortezomib, cyclophosphamide, and dexamethasone for a non-IgM monoclonal immunoglobulin and rituximab alone or in combination with cyclophosphamide and dexamethasone for an IgM monoclonal
Kan'shina, N F; Rykov, V A; Lakhno, P A
Clinico-anatomical data of a rare condition congenital oligomeganephronic renal hypoplasia with a glomerulonephritis as a complication are available for a 13-year-old girl who died of chronic renal failure. Large aglomerular zones consisting of primitive canaliculi in a loose stroma were observed in kidneys that were decreased in size. The glomeruli were few in number, some of them of a large size (2-2.5-fold), firmly attached to the capsule, with pronounced extracapillary proliferation.
Khoo, J J; Pee, S; Thevarajah, B; Yap, Y C; Chin, C K
There has been no published study of biopsy-proven childhood glomerulonephritis in Malaysia. To determine the pattern of childhood glomerulonephritis in Johor, Malaysia from a histopathological perspective and the various indications used for renal biopsy in children. Retrospective study was done of all renal biopsies from children under 16 years of age, received in Sultanah Aminah Hospital, Johor between 1994 and 2001. The histopathological findings were reviewed to determine the pattern of biopsy-proven glomerulonephritis. The indications for biopsy, mode of therapy given after biopsy and the clinical outcome were studied. 122 adequate biopsies were received, 9 children had repeat biopsies. Of the 113 biopsies, minimal change disease formed the most common histopathological diagnosis (40.7%) while lupus nephritis formed the most common secondary glomerulonephritis (23.0%). The main indications for biopsy were nephrotic syndrome (50.8%), lupus nephritis (25.4%) and renal impairment (13.1%). The mode of therapy was changed in 59.8% of the children. Of 106 patients followed-up, 84 children were found to have normal renal function in remission or on treatment. 4 patients developed chronic renal impairment and 16 reached end stage renal disease. Five of the 16 children with end stage disease had since died while 11 were on renal replacement therapy. Another 2 patients died of other complications. The pattern of childhood GN in our study tended to reflect the more severe renal parenchymal diseases in children and those requiring more aggressive treatment. This was because of our criteria of selection (indication) for renal biopsy. Renal biopsy where performed appropriately in selected children may not only be a useful investigative tool for histological diagnosis and prognosis but may help clinicians plan the optimal therapy for these children.
Ceri, Mevlut; Unverdi, Selman; Altay, Mustafa; Unverdi, Hatice; Ensari, Arzu; Duranay, Murat
Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease characterized by recurrent attacks of fever and painful episodes of sterile polyserositis. Kidney involvement may occur as a result of secondary amyloidosis during the course of FMF. Previously, different types of glomerulopathies such as IgM and IgA nephropathy, crescentic glomerulonephritis, diffuse proliferative glomerulonephritis, minimal change disease, and membranoproliferative glomerulonephritis were rarely reported. We herein represent a first case of membranous glomerulonephritis who had complete remission with colchicine treatment in the course of familial Mediterranean fever.
Yabuuchi, Junko; Suwabe, Tatsuya; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Hayami, Noriko; Oguro, Masahiko; Kunisawa, Kyohei; Kawada, Masahiro; Yamanouchi, Masayuki; Sumida, Keiichi; Mizuno, Hiroki; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi
We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis.
Yabuuchi, Junko; Suwabe, Tatsuya; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Hayami, Noriko; Oguro, Masahiko; Kunisawa, Kyohei; Kawada, Masahiro; Yamanouchi, Masayuki; Sumida, Keiichi; Mizuno, Hiroki; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi
We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis. PMID:27904866
Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja
We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.
Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja
We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353
Mantan, M.; Sethi, G. R.; Batra, V. V.
Glomerulonephritis develops in about 20% patients with infective endocarditis (IE), but is mostly asymptomatic. Heavy proteinuria or derangement of kidney functions is uncommon. We report here a child with IE and proliferative glomerulonephritis who manifested as significant proteinuria that recovered on treatment with immunosupressants. PMID:24049276
Ghosh, Biswadip; Pande, Arindam; Ghosh, Anirban; Banerjee, Arnab; Saha, Sandip
Membranous glomerulonephritis is rarely associated with tuberculosis infection. We report a case of a 24-year-old female with tuberculous peritonitis associated with membranous glomerulonephritis causing subnephrotic range proteinuria. Histological examination confirmed both diagnoses. The patient showed improvement with anti-tubercular drugs over six months of follow-up.
Akoglu, Hadim; Dede, Fatih; Akoglu, Gulsen; Gonul, Ipek Isik; Odabas, Ali Riza
Psoriasis is a hereditary, chronic inflammatory disorder of the skin. Generally, the psoriatic process is limited to the skin; however, internal organs such as the kidneys may be involved in the course. Several glomerular diseases have been distinguished due to renal histological findings of psoriatic patients to date. The underlying pathogenetic mechanisms of these associations remain unclear because of the limited number of cases. We report a case of primary membranoproliferative glomerulonephritis (MPGN) in a psoriatic patient. This is the first reported case that demonstrates the coexistence of MPGN and psoriasis.
Parker, M G; Atkins, M B; Ucci, A A; Levey, A S
Cytokines have been used in experimental and standard protocols for immune enhancement for cancer. The combination of interleukin-2 and interferon-alpha 2 beta has been used in experimental protocols for metastatic renal cell carcinoma. A man who developed rapidly progressive renal failure after receiving this combination therapy is reported. A renal biopsy revealed a pauci-immune crescentic glomerulonephritis. Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were absent. The spectrum of renal disease and potentially related extrarenal manifestations associated with interleukin-2 and inteferon-alpha are reviewed. A pathogenesis of altered cell-mediated immunity, consistent with abnormalities in extrarenal organs after immune enhancement, is proposed.
McAdoo, Stephen P; Bhangal, Gurjeet; Page, Theresa; Cook, H Terence; Pusey, Charles D; Tam, Frederick W K
Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.
Villar, I; Hernández, E; Cozzi, J; Paletta, C; Mathurín, S
A 32 year old man was admitted for dyspnea, hemoptysis, macroscopic hematuria, hypertension (140/100), peripheral edema and hemodynamic decompensation. Lung Xrays revealed pulmonary edema and a cavity in the left apex. Laboratory determinations revealed an altered renal function with increased creatinine and urea levels and nephrotic syndrome. There was leucocyturia, hematuria and cylindruria. The sputum showed a large number of acid-fast bacilli. The patient began anti-tuberculosis treatment with three drugs (isoniacid, rifampicin, pirazinamide). On ultrasonography, both kidneys revealed ecogenic lesions with size, shape and cortico-medular relationship preserved. The patient persisted with altered renal function, steady levels of urea nitrogen, creatinine and potassium, preserved diuresis and hypertension. Bidimensional echocardiogram: LVDD 55 mm, hypoquinetic septum, pericardic effusion, thickened pericardium, pleural effusion, shortening fraction decreased. He received treatment for this congestive cardiac failure and hypertension with enalapril, nifedipine and fursemide. A percutaneous renal biopsy was performed with anatomopathologic diagnosis of diffuse encocapillar proliferative glomerulonephritis with crescents (15%) and total glomerular sclerosis (33%). Immunofluorescence: positive, immune-complexes with IgM and C3. The patient gradually recovered his normal renal function, improved his pleural effusions and normalized his cardiac function. He was discharged in good clinical condition on the 69th day of anti-tuberculosis treatment. An association between pulmonary tuberculosis and glomerulonephritis is discussed. It is proposed that renal lesions might be the consequence of the tuberculosis due to the sedimentation of circulating immune-complexes.
Pillebout, Evangéline; Nochy, Dominique
IgA nephropathy is the primitive glomerulonephritis the most frequently encountered worldwide. In about one case out of three, it is responsible for the progression from progressive renal failure to end-stage renal failure. The pathophysiological mechanisms of this disease which is mediated by immune complexes remain unclear. The presentation, clinical progression and optical microscope aspect of the renal biopsy may widely vary, making any histological classification very difficult. Most therapeutic studies include the patients only on clinical criteria of severity. The only consensual management is that of patients with a nephropathy and mild glomerular lesions and a nephritic syndrome, or with an extracapillar glomerulonephritis and a rapidly progressive renal failure; corticoids are indicated in former cases while corticoids must be combined with immunosuppressive agents in the latter ones. Corticotherapy may be considered in patients with a proteinuria higher than 1g/day without renal failure. In any patient with primitive IgA nephropathy, the overall management used for chronic glomerulopathy must be initiated, including, in case of arterial hypertension or proteinuria, the renin-angiotensin system blockade.
Erlij, Daniel; Calderón, Beatriz; Rivera, Angela; Mella, Cristián; Valladares, Ximena; Roessler, Emilio; Rivera, María Teresa; Méndez, Gonzalo
Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.
Bussolati, B; Camussi, G
Recent experimental studies allowed the identification of several mechanisms of immune deposit formation, which are able to reproduce the morphological and clinical pattern of human glomerulonephritis. Moreover, it was shown that most of the lesions considered, in the past, as due to circulating immune complexes (IC), are instead caused by the "in situ" formation of IC. As a result of these studies, the following schematic classification was proposed: 1) immune deposits formed by glomerular localization of IC primarily formed in the circulation; 2) immune deposits formed "in situ" by reaction of circulating antibodies with fixed structural antigens; 3) immune deposits formed "in situ" by antibodies reactive with movable structural antigens; 4) immune deposits formed "in situ" by antibodies reactive with sequestered antigens leaking out of tissues; 5) IC formed "in situ" by antibodies reactive with exogenous or non-glomerular endogenous antigens planted in the glomeruli; 6) ANCA-associated glomerular disease.
Mukhin, I V; Nikolenko, V Iu
The influence of a systemic enzymotherapy on the morphological, biochemical, and functional manifestations of the kidney damage during the experimental gouty and primary glomerulonephritis is described in comparison to the results obtained by traditional methods.
Mukhin, I V
Patients with chronic glomerulonephritis (CG) develop disturbances of lipid blood spectrum leading to additional damage to renal structure. The existent methods of pathogenetic therapy have no effect on lipid imbalance. Recently, many autoimmune diseases have been treated with systemic enzyme therapy (SET). The authors studied SET effect in disturbed lipid metabolism in experimental glomerulonephritis. Experimental animals showed morphological and biochemical changes similar to those in CG of man. SET reduced renal tissue damage and symptoms of dyslipoproteinemia.
Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J
We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.
Kanaji, Nobuhiro; Kushida, Yoshio; Bandoh, Shuji; Ishii, Tomoya; Haba, Reiji; Tadokoro, Akira; Watanabe, Naoki; Takahama, Takayuki; Kita, Nobuyuki; Dobashi, Hiroaki; Matsunaga, Takuya
Male, 83 FINAL DIAGNOSIS: Membranous glomerulonephritis Symptoms: Producting cough Medication: - Clinical Procedure: - Specialty: Nephrology. Rare disease. Membranous glomerulonephritis can occur secondarily from infectious diseases. There are no reports describing membranous glomerulonephritis caused by non-tuberculous mycobacterium infection. However, several cases with membranous glomerulonephritis due to Mycobacterium tuberculosis have been reported. Mycobacterium shimoidei is an uncommon pathogen, and less than 20 cases with this species have been reported. A therapeutic regimen for this infection has not been established yet. An 83-year-old Japanese man presented with productive cough for 6 months. Computed tomography scan showed multiple cavities in the bilateral pulmonary fields. Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing. Urine examination showed a sub-nephrotic range of proteinuria and histology of the kidney showed membranous glomerulonephritis. Antimycobacterial treatment with clarithromycin, rifampicin, and ethambutol dramatically improved not only the pulmonary disease, but also the proteinuria. To the best of our knowledge, the presented case is the first report showing non-tuberculous mycobacterium-induced secondary membranous glomerulonephritis. A combination with clarithromycin, ethambutol, and rifampicin might be effective for treatment of Mycobacterium shimoidei infection.
Al Wakeel, Jamal S; Mitwalli, Ahmed H; Tarif, Nauman; Alam, Awatif A; Hammad, Durdana; Abu-Aisha, Hassan; Memon, Nawaz; Sulimani, Fathia; Askar, Akram; Qudsi, Abdo
Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the
Wagrowska-Danilewicz, M; Danilewicz, M; Fisiak, I; Piskorska, J
We report a case of IgA-dominant postinfectious glomerulonephritis in a 49-year-old man presenting with acute kidney injury, nephrotic range proteinuria and hematuria. He suffered from ischemic heart disease, cardiac insufficiency, mitral regurgitation, tricuspid insufficiency, septal aneurysm and hypertension. Renal biopsy revealed segmental and focal endocapillary and mesangial hypercellularity, and thickening of the glomerular capillary wall. Immunofluorescence showed co-dominant strong coarse granular immunostaining of IgA, IgG and C3 mainly along the glomerular capillary wall. On electron microscopy some large subepithelial hump-shaped deposits were present. In summary, this case demonstrates the presence of a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis.
Rashid, H U; Papiha, S S; Agroyannis, B; Morley, A R; Ward, M K; Roberts, D F; Kerr, D N
One hundred and seventy-nine patients with various forms of glomerulonephritis confirmed histologically were tested for HLA A and B antigens: Thirty-four with membranous glomerulonephritis were also typed for DR antigens. One hundred and forty-one of these patients were further tested for blood group, red cell enzyme, and plasma protein systems. The minimal-change and the mesangio-capillary glomerulonephritis showed a significant association with B8 and Bw44 antigens respectively, whereas the membranous nephritis in addition to B8 was also found to be associated with DR3 antigen. Previously described associations with Henoch-Schönlein and Berger's nephritis were not proved. A large group with nonspecific proliferative glomerulonephritis did not show any association with HLA. Among the other single-gene characters studied, a significant association was found with Bf (Factor B or C3 proactivator) and adenosine deaminase, both markers thought to be involved in the immune response. The close association of the markers located on chromosome 6 and glomerulonephritis indicates that there may be an immunological component in the aetiology of the disease. The significance of the various associations found is discussed.
Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev
Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.
Danielsen, H; Kornerup, H J; Olsen, S; Posborg, V
310 cases of glomerulonephritis classified morphologically according to the criteria of the WHO were analyzed retrospectively in order to determine the frequency of arterial hypertension. The overall prevalence of arterial hypertension was 61%. Hypertension was most frequent and severe in membranoproliferative and sclerotic glomerulonephritis, but often mild and transient in extracapillary glomerulonephritis. Hypertension usually developed during the early stages of the disease when kidney function was well preserved and in only 16% was hypertension first seen during the uremic stage. No correlation was found between hypertension and the presence of the nephrotic syndrome. During dialysis, hypertension was present in 78%; in 90% of these patients hypertension was "controllable" and in 10% it was "uncontrollable".
Ghosh, Gopal Chandra; Sharma, Brijesh; Katageri, Bhimarey; Bhardwaj, Minakshi
Glomerulonephritis (GN) is an immunological phenomenon in bacterial endocarditis. These may be pauci-immune/vasculitic GN, post-infective GN, and sub-endothelial membranoproliferative glomerulonephritis. Each type of glomerulonephritis usually occurs in isolation. We report a case of infective endocarditis with dual existence of pauci-immune/vasculitic GN and post infective type of GN at the same time.
Jennette, J. C.; Wilkman, A. S.; Falk, R. J.
Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2683800
Smith, S M; Hoy, W E; Pathak, D; Megill, D M; Tung, K S; Hughson, M D
Immune complex-associated mesangiopathic glomerulonephritis was found in 64% of renal biopsies performed on Navajos over a 16-year period. It is characterized by mild mesangial expansion and predominant immunoglobulin (Ig) A and/or IgM deposits. Statistical analysis shows that glomerular deposits of IgG and C3, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and tubular atrophy are associated with renal insufficiency at the time of biopsy, and can be integrated into a pathologic index that has a high correlative value. Mesangiopathic glomerulonephritis is probably responsible for the high rates of non-diabetic end-stage renal disease seen in Navajo Indians.
Takahashi, K; Suda, S; Takayama, M; Deguchi, F; Matsuda, O; Tachibana, K; Yoshimura, A
The main target organs of myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA)-related disease are the kidney and lung. This report describes a 71-year-old man with rapidly progressive glomerulonephritis (RPGN) and interstitial pneumonitis associated with MPO ANCA. The patient was admitted to our hospital because of bloody sputum, low grade fever and appetite loss on October, 1998. He was diagnosed as having interstitial pneumonitis from the findings of chest X-ray and CT examinations. Moderate proteinuria and hematuria, renal dysfunction(serum creatinine: 5.6 mg/dl, BUN: 58.0 mg/dl) and positivity for MPO ANCA were noted. He was negative for anti-glomerular antibody and PR3-ANCA. Renal biopsy was performed and revealed crescentic glomerulonephritis without deposition of immunoglobulins. Therefore, the diagnosis of pauci immune type RPGN was made. Pulse therapy with methylprednisolone(1.0 g/day x 3 days) following oral administration of prednisolone (60 mg/day) found marked improvement of renal function maintenance and interstitial pneumonitis, respectively. However, he died because of lung tuberculosis and acute tuberculous pericarditis during treatment with prednisolone. In this case, MPO ANCA might have been directly associated with both RPGN and interstitial pneumonitis. Furthermore, chronic lung disease, such as interstitial pneumonitis, is important as a preceding disease of RPGN. MPO ANCA-related disease is more frequent in aged persons, therefore particular attention should be paid during their treatment with an immunosuppressant.
Kunjal, Ryan; Makary, Raafat; Poenariu, Andreea
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management. PMID:27293925
Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Chang, Anthony; Mohan, Chandra; Larin, Kirill V
Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.
Alexopoulos, Efstathios; Gionanlis, Lazaros; Papayianni, Ekaterini; Kokolina, Elizabeth; Leontsini, Maria; Memmos, Dimitrios
Background Small vessel vasculitides are known to follow a devastating course towards end-stage renal disease, unless treated with immunosuppressive regiments. We investigated the value of clinical, histological and immunohistochemical parameters as predictors of outcome at diagnosis in patients with pauci immune necrotizing glomerulonephritis. Methods In 34 patients the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial infiltration, interstial fibrosis and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, α-SMA(+) and PCNA(+) cells, the expression of integrins α3β1 and LFA-1β, the adhesion molecule ICAM-1, the growth factor TGF-β1 and the terminal complement component C5b-9. Results 24 pts (70.6%) showed a complete or partial response to the treatment. The follow-up period was 20 ± 22 months. At multivariate analysis, serum CRP (p = 0.024), the intensity of tubular expression of C5b-9 (p < 0.0001) as well as the extent of glomerular and tubular expression of α3β1 integrin (p = 0.001 and 0.008 respectively) independently predicted the response to treatment. The response rate was better in ANCA(+) pts (p = 0.008). The extent of interstitial infiltrate (p < 0.0001), the severity of tubulointerstitial fibrosis (p < 0.0001) and the severity of tubular TGF-β1 expression (p < 0.0001) were independent predictors of long term outcome of renal function. Conclusion Patients with ANCA-associated renal vasculitis seem to respond better to the treatment. Acute phase reactants, such as CRP, implying a more intense parenchymal inflammatory reaction, as well as the intensity of the de novo expression of C5b-9 and the glomerular and tubular expression of α3β1 integrin predict the response to therapy. The severity of TIN lesions and of the tubulo-interstitial TGF-β1 and C5b-9 expression predict an
Gadde, Shilpa; Lee, Belinda; Kidd, Laura; Zhang, Rubin
Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis (RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine (adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis. PMID:27872837
The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect. PMID:26877924
The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect.
Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel
C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.
Ueno, Kazuyuki; Shimizu, Masaki; Yokoyama, Tadafumi; Ishikawa, Sayaka; Tasaki, Yuko; Inoue, Natsumi; Sugimoto, Naotoshi; Ohta, Kazuhide; Yachie, Akihiro
To clarify in vivo neopterin expression within the human kidney and its clinical role as a biomarker for immune complex-mediated mesangial proliferative glomerulonephritis (mesPGN) in children. We examined neopterin expression within the kidneys of 14 patients with mesPGN and five patients with minimal changes. We also measured the serum and urinary neopterin levels in fourteen patients with mesPGN and sixteen age-matched healthy controls and correlated the histological findings and clinical features. Neopterin expression was observed within the distal tubular epithelial cells. It was induced within the glomerular endothelial cells and infiltrated CD68-positive macrophages in the glomeruli and interstitial areas. Furthermore, urinary neopterin levels were significantly elevated and positively correlated with histopathological findings and the degree of proteinuria. These findings indicate that increased urinary neopterin may reflect macrophage activation and active inflammation within the kidney in immune complex-mediated glomerulonephritis. Neopterin may thus represent a useful biomarker of immune complex-mediated glomerulonephritis in the clinical setting.
Cherif, Mejda; Hedri, Hafedh; Ounissi, Mondher; Gergah, Taher; Goucha, Rim; Barbouch, Samia; Abderrahim, Ezzedine; Maiz, Hedi Ben; Kheder, Adel
Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression.
Seelig, H P; Seelig, R; Fischer, K; Maurer, R; Safer, A; Schnitzlein, W
The nephrotic syndrome presumably caused by an immune complex glomerulonephritis constitutes a major side effect attendant upon chronic administration of penicillamine. The possible induction of an immune-complex glomerulonephritis by penicillamine and its further development after stopping the drug was investigated in rats. --60 rats were fed perorally 2000 mg D-Penicillamine/kg BW/die resp. for a period of 8--44 days. Following unilateral nephrectomy the animals were observed for further 5 weeks. --Dependent to the time of penicillamine application there was an increasing deposition of IgG and C3 in a granular pattern along the glomerular basement membrane and within the mesangium. The IgG deposits initially were focal and segmental later on diffuse and global in distribution. 5 weeks after stopping the penicillamine the immune globulin deposits had disappeared completely or at least in part as did the mild focal glomerulonephritis and the moderate proteinuria which developed in some animals after a 44 day treatment with penicillamine. --The results confirm the hitherto presumed immune complex pathogenesis of the penicillamine induced nephropathy. The disappearance of the immunoglobulins deposited and of proteinuria stopping penicillamine alludes the good prognosis of this kind of nephropathy.
Bolton, W. Kline; Chen, Lanlin; Hellmark, Thomas; Fox, Jay; Wieslander, Jorgen
Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of α3 type IV collagen (α3(IV)NC1) and non-nephritogenic α1(IV)NC1. CPs with aminoterminal α3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an α1(IV)NC1 CP with 69AA of α3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an α1(IV)NC1 with nine AA of α3(IV)NC1 (binding). GBM, S2 and D3 induced EAG. GBM immunized rats had intense IgG deposits but S2 and D3 rats had minimal deposits. A 13 mer rat peptide encompassing the aminoterminal site induced EAG sans antibody, while peptides not encompassing the region failed to induce GN. Asparagine at position 19 rather than isoleucine was essential for disease induction. These studies define critical limited AA sequences of α3(IV)NC1 associated with glomerulonephritis without antibody, and demonstrate that this region contains a T-cell epitope responsible for induction of glomerulonephritis. PMID:16555617
Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio
The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio
The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.
Tabata, Nobuko; Yoshizawa, Hideka
Generalized pustular lesions characterized by acute onset with fever occur in pustulosis acuta generalisata, acute generalized exanthematous pustulosis, and generalized pustular psoriasis. In the present report, we describe a pediatric case of generalized pustular eruption that was not completely consistent with clinical features. Our patient had no evidence of a post-streptococcal infection. We observed scattered symmetric eruption of discrete pustules with an inflammatory halo on normal skin. The eruption was absent on her palms and soles of the feet. To the best of our knowledge, there are no reports in the English literature of cases with clinical features similar to those of our patient. PMID:27462226
Sun, L; Yuan, Q; Feng, J; Yao, L; Fan, Q; Ma, J; Wang, L
Mycobacterium tuberculosis infection causing glomerulonephritis is a rare disorder. This retrospective study analyzed the clinical characteristics of patients diagnosed with tuberculosis-mediated glomerulonephritis (TB-GN) between 2002 and 2009, as well as the diagnostic tools used. These findings were then compared with those of patients with primary glomerulonephritis (P-GN). The records of all patients were reviewed. The diagnosis of TB-GN was based on renal hematuria and/or proteinuria and cure after antituberculosis therapy alone plus urine culture positive for M. tuberculosis, demonstration of typical tubercle granulomas on renal biopsy specimens, or the detection of M. tuberculosis DNA by polymerase chain reaction (PCR) on renal specimens. Forty-six patients with TB-GN and 49 patients with P-GN were included. Compared with patients in the P-GN group, most (76%) patients with TB-GN had a history of TB. Systemic symptoms were much more frequent in patients with TB-GN than local genitourinary symptoms. Serological testing showed a statistical difference between the two groups. Immunoglobulin A nephropathy was found in the majority (72%) of patients with TB-GN. M. tuberculosis DNA detection was positive in 39 (84.8%) patients, a much higher positive rate of diagnosis than that with urine culture for M. tuberculosis. The manifestation of TB-GN is atypical and nonspecific. It warrants a high index of suspicion when patients with renal hematuria and proteinuria fail to respond to standard treatments for P-GN. Clinicians should pay close attention to the medical history and results of special laboratory tests. M. tuberculosis DNA detection on renal biopsy specimens should be considered in order to confirm the diagnosis of TB-GN.
Kurosu, Akira; Oka, Noriko; Hamaguchi, Takeshi; Yoshikawa, Norishige; Joh, Kensuke
Immunoglobulin A nephropathy (IgAN) showing predominant IgA and complement 3 (C3) deposition on the mesangium is an immune complex-mediated glomerulonephritis. This renal disease is the most common primary glomerular disease worldwide. However, infantile onset of IgAN is rare. In the present patient, urinary protein and occult blood were detected in a girl aged 1 year and 8 months on urinalysis at a nursery school. Despite being young, a kidney biopsy was performed for diagnosis and the correct choice of therapy. Glomerular mesangial cell proliferation and a double contour of the glomerular basement membrane (GBM) resembling a railroad track were noted on light microscopy. Therefore, the patient was diagnosed morphologically with membranoproliferative glomerulonephritis (MPGN), because mesangial hypercellularity and thickening of the GBM were identified. However, on immunofluorescent staining, the deposition of immune complexes mainly consisting of IgA, IgG, and C3 was noted in the mesangial region and glomerular capillary loops. On electron microscopy, electron-dense deposits were recognized in the subendothelial and paramesangial regions associated with mesangial cell interposition into the subendothelial space. Autoimmune diseases and infection-associated secondary glomerulonephritis were clinically excluded, because there were no relevant signs or symptoms. Steroid treatment was initiated and findings of urinalysis were normalized within 8 months. This patient was finally diagnosed with IgA nephropathy showing the features of MPGN. The present patient was the youngest among reported cases of IgA nephropathy, suggesting that early onset of IgAN is associated with an MPGN-like lesion. The present report provides information for pathogenesis of IgA nephropathy.
Mukhin, I V
There is formation of free radicals in mesangial cells in patients with chronic glomerulonephritis which increases destruction of renal tissue and enable autoimmune inflammation. The unbalance between activity of oxidizing and antioxidazing starts developing. It accelerates the progression of the disease. The article presents the assessment of influence of enzyme medication Wobenzym on main indices of oxidizing and antioxidazing systems. It was established the presence of antioxidant effect in Wobenzym medication. The use of this medication in combination with other drugs and without them enables restoration of the disturbed balance.
Podorol'skaia, L V; Andreenko, G V; Poliantseva, L R; Bumblite, I D
Functional activities of plasminogen activators (FPAA) and their inhibitors and plasminogen activators's (PA), antigen level were determined in 31 patients with chronic glomerulonephritis, 23 patients with amyloidosis and 15 healthy persons. High FPAA correlated with favourable prognosis of diseases, elevated PA antigen level and diminished alpha 1-antitrypsin, alpha 2-macroglobulin and antiactivator activities. There were decreased PA antigen level and increased inhibitor's activities in group with zero FPAA. Protein loaded functional probe demonstrated the presence of PA reserves in high FPAA patients and "pathological proteolysis" in zero FPAA patients. The last phenomenon was likely connected to nonspecific proteases differed from PA.
Gowda, K K; Joshi, K; Ramachandran, R; Nada, R
A 40-year-old male presented with nephrotic syndrome. Light microscopic analysis of the renal biopsy showed thickening of the glomerular capillary wall. Immunofluorescence examination revealed granular deposition of monoclonal immunoglobulin (Ig) G3-kappa and complement C3 along the glomerular basement membrane. Electron microscopy showed subepithelial electron dense deposits, thus confirming membranous glomerulonephritis (MGN) with monoclonal gammopathy. MGN with monoclonal gammopathy is an extremely rare but distinctive entity. This patient was treated with a combination of bortezomib, thalidomide and dexamethasone and showed partial remission of his nephrotic state and dysproteinemia.
Wardle, E. N.; Menon, I. S.; Rastogi, S. P.
Plasma and urine fibrinolysis were studied in 36 patients with glomerulonephritis and proteinuria. In 40% of these plasma fibrinolytic activator activity was moderately reduced and fibrinolytic inhibitors were increased. Globulins with antiplasmin effect were raised, particularly in the earlier months. Both the serum cholesterol and the plasma fibrinogen were related to the level of serum albumin, and those patients with high fibrinogen levels were also those with poor plasma fibrinolytic activator and those showing a steady deterioration. Urinary fibrinolysis was greatly reduced in most patients and bore no relation to plasma fibrinolysis levels. Hence urokinase is not derived from circulating plasminogen activator. PMID:4246192
Fujiwara, Takashi; Komatsuda, Atsushi; Ohtani, Hiroshi; Togashi, Masaru; Sawada, Ken-Ichi; Wakui, Hideki
A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.
Andres, Giuseppe A.; Accinni, Lidia; Hsu, Konrad C.; Zabriskie, John B.; Seegal, Beatrice C.
1. Kidney biopsies from 4 cases of severe acute glomerulonephritis were obtained 11 to 25 days after the onset of clinical manifestations of the disease. These tissues were treated with ferritin-conjugated antibodies to 7S γ-globulin, β1C, and Type 12 streptococcal products. Adjacent pieces of the biopsied material were treated with control ferritin-labeled antisera or with ferritin alone. As further controls, normal renal tissue and renal tissue from patients with other kidney diseases were treated with the same antisera. The 3 antisera to 7S γ-globulin, β1C and Type 12 streptococcus were specifically bound in electron-opaque foreign material in the following renal areas: (a) the lumen of glomerular capillaries; (b) medullary arteriolar walls (2 cases); (c) pinocytic vacuoles and absorption droplets of endothelial or mesangial cells; (d) canals between proliferating mesangial or endothelial cells which connect the capillary lumen with the deep mesangial region or with the endothelial side of the basement membrane; (e) basement membrane proper; (f) subendothelial and certain subepithelial deposits; and (g) Bowman's space. 2. None of the 3 ferritin-conjugated antisera listed above were bound to the nuclei of glomerular cells or to portions of the cytoplasm other than those specified. 3. Ferritin-conjugated antisera to pneumococcus Type II and vaccinia virus and ferritin alone were not bound to any structures in the glomerular tissue. 4. None of the ferritin-conjugated antisera bound to normal renal tissue or to kidney tissue from other renal disease. 5. The data obtained are compatible with the following working hypothesis: Antigen-antibody aggregates of Type 12 streptococcal products, γ-globulin, and complement are present in the circulating blood of patients with severe acute glomerulonephritis. Large amounts of the complexes are caught in the filtering system of the glomeruli. The inflammatory reactions seen in the glomerular structures result from the
Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed. PMID:28573137
Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is complex. Intricacy arises from factors such as autoimmunity, cancer and structural abnormalities within the kidney. Studies using animal models have highlighted crucial interaction between inflammatory cells and cells intrinsic to the kidney, both of which are fundamental to the pathogenesis of GN. This review aims to provide insight on a 'suitable' model for nephrotoxic nephritis and glomerulonephritis (NTN GN) and relate its experimental validity to humans. The BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic options for patients with GN and subsets thereof. Currently used immunosuppressive therapies for GN are not always uniformly effective and are frequently associated with serious side-effects. Corticosteroids are effective in several types of GN owing to their ability to inhibit the pro-inflammatory effects of cytokines known to promote glomerular inflammation. Differences between experimental and human GN complicate translation of experimental therapies into practice. More research is required to translate animal model research into a better comprehension of human GN disease. However, the complexity of GN research makes findings a challenge to replicate.
Lawler, W; Williams, G; Tarpey, P; Mallick, N P
Twenty-three cases of IgM associated primary diffuse mesangial proliferative glomerulonephritis are presented. In 18, IgM was the sole localising host immunoglobulin, and it was the predominant globulin in five; C3 was also present in 18. Light microscopy revealed variable diffuse and global mesangial proliferation in all cases, with additional focal global sclerosis in 16, focal segmental sclerosis in 15, and small capsular crescents in seven. Material for electron microscopy was available from 19 patients; in 13, occasional intramesangial electron dense deposits were identified, and in 18 there were irregular, rather ill defined areas of increased electron density in mesangial regions. Clinically, 14 patients presented with the nephrotic syndrome, and nine had asymptomatic proteinuria. During follow-up, only 10 patients showed no change in renal function or improved; the remainder showed increasing hypertension and/or renal function deterioration and four developed end stage renal failure. It is suggested that IgM associated mesangial proliferative glomerulonephritis should be considered as a distinct clinicoimmunopathological entity. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7002957
Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY
Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617
Soto, K; Wu, Y L; Ortiz, A; Aparício, S R; Yu, C Y
Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. Copyright © 2010 Elsevier Inc. All rights reserved.
Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K.
Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208
Faurie, R E; Prado, A C
The relationship between streptococcal infection and renal disease has been object of multiple studies. Streptococcal infection may induce acute glomerulonephritis or interstitial nephritis. We report a patient with a streptococcal infection who developed acute renal failure. The renal biopsy showed an acute interstitial nephritis, with an interstitium infiltrate with a significant number of eosinophils. We review the causes of acute renal failure associated with streptococcal infection, specially acute interstitial nephritis.
... a strep infection and if you might have rheumatic fever or kidney problems ( glomerulonephritis ) due to that infection. ... Read More Antibody Antigen Post-streptococcal glomerulonephritis (GN) Rheumatic fever Review Date 5/1/2015 Updated by: Jatin ...
Nakada, Yasuyuki; Tsuboi, Nobuo; Takahashi, Yasuto; Yoshida, Hiraku; Hara, Yoriko; Okonogi, Hideo; Kawamura, Tetsuya; Arimura, Yoshihiro; Yokoo, Takashi
We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immunofluorescence examination of the patient's neutrophils showed a perinuclear pattern. Enzyme-linked immunosorbent assays revealed that the ANCA in this case did not target myeloperoxidase (MPO) or proteinase 3 (PR3) but bactericidal-/permeability-increasing protein, elastase, and lysosome. The relationship between these two etiologically distinct entities, MPO-/PR3-negative ANCA-associated glomerulonephritis and MGN, remains unclear. PMID:25648906
Maduell, F; Sánchez-Alcaraz, A; Sigüenza, F; Caridad, A; Sangrador, G
Recent reports suggest that cyclosporin A is beneficial in inducing remission of idiopathic nephrotic syndrome. Nephrotic syndrome is seen in 10-30% of patients with rapidly progressive glomerulonephritis. We report a case of a 69-year-old man with nephrotic syndrome, associated with idiopathic rapidly progressive glomerulonephritis, who was treated initially with corticosteroid and cyclophosphamide. Three months later he developed thrombophlebitis and leucopenia and cyclophosphamide was suspended. Relapse of nephrotic syndrome associated with rapidly progressive glomerulonephritis developed and therapy with cyclosporin A was used with a good response.
Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Mohammadzai, Qais; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Chang, Anthony; Mohan, Chandra; Larin, Kirill V.
Acute Glomerulonephritis caused by anti-glomerular basement membrane disease has a high mortality due to delayed diagnosis. Thus, an accurate and early diagnosis is critical for preserving renal function. Currently, blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution. Optical coherence tomography (OCT) is a noninvasive imaging technique that provides superior spatial resolution (micron scale) as compared to ultrasound and CT. Pathological changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signal, such as optical attenuation and speckle variance. Moreover, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, we utilized OCT to detect the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, classification accuracy using only optical metrics was clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improved from 76% to 95%. These results show that OCT combined with OCE can be potentially useful for nephritis detection.
Yashima, Akihito; Mizuno, Masashi; Yuzawa, Yukio; Shimada, Koki; Suzuki, Norihiko; Tawada, Hideo; Sato, Waichi; Tsuboi, Naotake; Maruyama, Shoichi; Ito, Yasuhiko; Matsuo, Seiichi; Ohno, Tamio
Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed mesangial proliferative glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.
Zhou, Hui; Chen, Min; Zhu, Ying; Wang, Bing; Liu, Xiao-ning; Zuo, Zhi; Tang, Feng-Ying
End-stage renal disease (ESRD) was defined as start of renal replacement therapy or death due to kidney disease. However, death due to acute kidney injury was not included. It typically occurs when chronic renal failure progresses to a point where the kidneys are permanently functioning at less than 10% of their capacity. Oxidative stress (OS) plays a crucial role in ESRD. Nicotinamide adenine dinucleotide phosphate (NADPH) is one of the most important enzymes during oxidative stress. Cytochrome b light chain (CYBA), encoded by a polymorphic gene, which is a critical component of the nicotinamide adenine dinucleotide (NADH)/NADPH oxidase system and plays an important role in electron transport and superoxide anion production, is located on chromosome band 16q24 and has six exons spanning almost 7.76 kb of genomic DNA. CYBA gene polymorphisms can influence the activity of NADPH oxidase. To evaluate the association between CYBA gene polymorphisms and ESRD, we genotyped five CYBA polymorphisms using TaqMan allelic discrimination assay on DNA samples from 306 healthy controls and 332 patients with ESRD. Our results suggested that rs1049255 polymorphism of CYBA modified the risk of ESRD (p = 0.019; OR = 0.625; 95%CI = 0.424-0.921). GG genotype and G allele might be a protective factor against the risk of ESRD, especially in patients with chronic glomerulonephritis.
Baba, Hiroshi; Kudo, Tomoo; Makino, Yoshinori; Mochizuki, Yasumasa; Takagi, Takayo; Une, Yumi
Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman's capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits.
BABA, Hiroshi; KUDO, Tomoo; MAKINO, Yoshinori; MOCHIZUKI, Yasumasa; TAKAGI, Takayo; UNE, Yumi
ABSTRACT Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman’s capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits. PMID:23856758
Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine
Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.
Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon
A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033
Chaurasia, Jai Kumar; Soni, Mayank; Ahmed, Murad; Naim, Mohammed
A 5-month-old male infant presented with a 15 day history of distension of abdomen. On clinical examination, a soft lump was palpable in the left lumbar region. Radiological findings suggested an enlarged non-functional left kidney with ureteropelvic adhesive obstruction. The left renal mass was excised and submitted for histopathological examination. The excised renal mass was cystic with its wall partly white and partly blue. Gross and histopathological findings were diagnostic of a white-blue pyelocalyceal cyst with hydrotic glomerulonephritis. This entity needs to be differentiated from a large number of other cystic diseases of the kidney. Intrauterine screening and diagnosis may be significant for a possible early intrauterine uro-laparoscopic recanalisation of the pyeloureteral obstruction to save the affected kidney.
Kawasaki, Y; Suzuki, J; Nozawa, R; Suzuki, H
Aims: In order to evaluate the efficacy of a school urinary screening programme, children with membranoproliferative glomerulonephritis (MPGN) type 1 were studied. Methods: A total of 52 patients who had been diagnosed with MPGN type 1 from 1970 to 1997 were studied; 35 were identified after 1974 on screening (group S), and 17 were identified by presenting symptoms (group N), mostly before 1989. Results: Mean blood pressure was 89 mm Hg in group S and 104 mm Hg in group N; urinary protein excretion was 0.9 g/day in group S and 3.0 g/day in group N. Histopathological evidence of chronic changes was found in six group S and 15 group N patients. No patients in group S had renal insufficiency, but five patients in group N required regular haemodialysis. Conclusions: Results suggest that early identification by school urinary screening may enable early management and so improve prognosis of MPGN. PMID:11806875
Ray, Susan; Rouse, Kelly; Appis, Andrew; Novak, Robert; Haller, Nairmeen Awad
Fibrillary glomerulonephritis (FGN) is a relatively rare cause of renal disease, found in only 0.6-1.5% of native renal biopsies. The pathogenesis of FGN is not well described, and very few associations with disease processes other than hepatitis C virus (HCV) have been made. We describe a case that provides evidence in support of the FGN-HCV association, as well as introduces the association of FGN-HCV and hypocomplementemia. The case is a 53-year-old African-American female demonstrating a classical presentation of FGN complicated by a concomitant HCV infection. Treating an HCV infection with alpha-interferon has been shown to result in subsequent improvement in the nephrotic syndrome and renal function. However, this patient is unique in that she is complicated with hypocomplementemia, creating a complex treatment situation.
Chen, Jin-Shuen; Chang, Li-Chien; Huang, Shyh-Jer
The importance of B-cell activation and immune complex-mediated Fc-receptor activation in the pathogenesis of immunologically mediated glomerulonephritis has long been recognized. The two nonreceptor tyrosine kinases, spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk), are primarily expressed by hematopoietic cells, and participate in B-cell-receptor- and Fc-receptor-mediated activation. Pharmacological inhibitors of Syk or Btk are undergoing preclinical development and clinical trials for several immune diseases; and Syk inhibitors have been shown to reduce disease activity in rheumatoid arthritis patients. However, the clinical therapeutic efficacies of these inhibitors in glomerulonephritis have not been evaluated. Herein, we review recent studies of Syk and Btk inhibitors in several experimental primary and secondary glomerulonephritis models. These inhibitors suppressed development of glomerular injury, and also ameliorated established kidney disease. Thus, targeting Syk and Btk signaling pathways is a potential therapeutic strategy for glomerulonephritis, and further evaluation is recommended. PMID:24795896
Cybulsky, Andrey V; Walsh, Michael; Knoll, Greg; Hladunewich, Michelle; Bargman, Joanne; Reich, Heather; Humar, Atul; Samuel, Susan; Bitzan, Martin; Zappitelli, Michael; Dart, Allison; Mammen, Cherry; Pinsk, Maury; Muirhead, Norman
The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of adult nephrologists reviewed the guideline statements for management of glomerular disease in adults and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas for which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the choice of second-line agents, are discussed in more detail. Existing practice variation also is addressed. The relevance of treatment recommendations to the Canadian practitioner is discussed.
Van Haare Heijmeijer, Sophie; Wilmes, Dunja; Aydin, Selda; Clerckx, Caroline; Labriola, Laura
Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID:26819786
Alexander, Jessy J; Chaves, Lee D; Chang, Anthony; Jacob, Alexander; Ritchie, Maria; Quigg, Richard J
In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH(-/-) mice chimeric for wild-type, CfH(-/-), CD11b(-/-), or FcRγ(-/-) bone marrow stem cells. Glomerulonephritis was worse in CD11b(-/-) chimeras compared with all others, whereas disease in FcRγ(-/-) and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b(-/-) chimeras had significantly more M1 macrophages and CD4(+) T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c(+) cells were similar in all experimental groups. CD11b(+) cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b(-/-) chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4(+) T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.
Kucherenko, A G; Markov, Kh M; Zokirov, N Z; Naumova, V I
A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.
Sowa, Mandy; Trezzi, Barbara; Hiemann, Rico; Schierack, Peter; Grossmann, Kai; Scholz, Juliane; Somma, Valentina; Sinico, Renato Alberto; Roggenbuck, Dirk; Radice, Antonella
Rapidly progressive glomerulonephritis (RPGN) is mainly caused by anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis, immune-complex or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides and leads to rapid loss of renal function. Detection of ANCA and autoantibodies (autoAbs) to GBM and dsDNA enables early diagnosis and appropriate treatment of RPGN aiding in preventing end-stage renal disease.Determination of ANCA on neutrophils (ANCA) as well as autoAbs to myeloperoxidase (MPO-ANCA), proteinase 3 (PR3-ANCA), GBM, and dsDNA was performed by the novel multiplex CytoBead technology combining cell- and microbead-based autoAb analyses by automated indirect immunofluorescence (IIF). Forty patients with granulomatosis with polyangiitis (GPA), 48 with microscopic polyangiitis (MPA), 2 with eosinophilic GPA, 42 with systemic lupus erythematosus (SLE), 43 with Goodpasture syndrome (GPS), 57 with infectious diseases (INF), and 55 healthy subjects (HS) were analyzed and findings compared with classical single testing.The CytoBead assay revealed for GPA, MPA, GPS, and SLE the following diagnostic sensitivities and for HS and INF the corresponding specificities: PR3-ANCA, 85.0% and 100.0%; MPO-ANCA, 77.1% and 99.1%; anti-GBM autoAb, 88.4% and 96.4%; anti-dsDNA autoAb, 83.3% and 97.3%; ANCA, 91.1% and 99.1%, respectively. Agreement with classical enzyme-linked immunosorbent assay and IIF was very good for anti-GBM autoAb, MPO-ANCA, PR3-ANCA, and ANCA, respectively. Anti-dsDNA autoAb comparative analysis demonstrated fair agreement only and a significant difference (P = 0.0001).The CytoBead technology provides a unique multiplex reaction environment for simultaneous RPGN-specific autoAb testing. CytoBead RPGN assay is a promising alternative to time-consuming single parameter analysis and, thus, is well suited for emergency situations.
Sowa, Mandy; Trezzi, Barbara; Hiemann, Rico; Schierack, Peter; Grossmann, Kai; Scholz, Juliane; Somma, Valentina; Sinico, Renato Alberto; Roggenbuck, Dirk; Radice, Antonella
Abstract Rapidly progressive glomerulonephritis (RPGN) is mainly caused by anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis, immune-complex or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides and leads to rapid loss of renal function. Detection of ANCA and autoantibodies (autoAbs) to GBM and dsDNA enables early diagnosis and appropriate treatment of RPGN aiding in preventing end-stage renal disease. Determination of ANCA on neutrophils (ANCA) as well as autoAbs to myeloperoxidase (MPO-ANCA), proteinase 3 (PR3-ANCA), GBM, and dsDNA was performed by the novel multiplex CytoBead technology combining cell- and microbead-based autoAb analyses by automated indirect immunofluorescence (IIF). Forty patients with granulomatosis with polyangiitis (GPA), 48 with microscopic polyangiitis (MPA), 2 with eosinophilic GPA, 42 with systemic lupus erythematosus (SLE), 43 with Goodpasture syndrome (GPS), 57 with infectious diseases (INF), and 55 healthy subjects (HS) were analyzed and findings compared with classical single testing. The CytoBead assay revealed for GPA, MPA, GPS, and SLE the following diagnostic sensitivities and for HS and INF the corresponding specificities: PR3-ANCA, 85.0% and 100.0%; MPO-ANCA, 77.1% and 99.1%; anti-GBM autoAb, 88.4% and 96.4%; anti-dsDNA autoAb, 83.3% and 97.3%; ANCA, 91.1% and 99.1%, respectively. Agreement with classical enzyme-linked immunosorbent assay and IIF was very good for anti-GBM autoAb, MPO-ANCA, PR3-ANCA, and ANCA, respectively. Anti-dsDNA autoAb comparative analysis demonstrated fair agreement only and a significant difference (P = 0.0001). The CytoBead technology provides a unique multiplex reaction environment for simultaneous RPGN-specific autoAb testing. CytoBead RPGN assay is a promising alternative to time-consuming single parameter analysis and, thus, is well suited for emergency situations. PMID:27858870
Huraib, Sameer O; Qureshi, Junaid I; Quadri, Khaja Hm; Al Flaiw, Ahmed; Al Ghamdi, Ghormullah; Jumani, Abdulqadir; Al Hejaili, Fayez; Raza, Hammad; Al Johani, Abdulaziz; Al-Katheri, Abdulmalik; Al-Khader, Abdullah A
Mycophenolate Mofetil MMF has been widely used in post-transplant immunosuppression. Its role is emerging in GN. MMF demonstrated promising results compared with cyclosphosphamide in stage IV lupus nephritis, in a recently published trial. It has been found to have a wide safety profile, with mostly gastroinetestinal side effects, which can be avoided through titration. Its action is through inhibition of the enzyme IMDPH (ionosine monophosphate dehydrogenase), leading to purine antagonism and inhibition of lymphocytes. We were aiming to demonstrate the efficacy of MMF in our GN population. In this study, we reviewed 17 patients who received MMF (dose - 1 gm po bid) for the past year. They were only included if it was given for the management of resistant primary glomerulonephritis. Complete remission has been defined as proteinuria of less than 0.5 g/day and partial remission as a reduction of proteinuria 50% of starting MMF therapy; all 17 MMF therapy patients uniformly achieved good BP ((29%) achieved complete remission and this group consisted of 1 membranous GN, 2 lupus GN (type IV and membranous), one FSGS and one with MPGN. Four of 17 (23%) were non-responders to therapy. This group articles.aspx? id=41 to side effects. We conclude that the MMF appears to be an effective alternate treatment modality in resistant membranous GN, lupus nephritis (type IV and V) and possibly MPGN, and to a lesser extent in resistant FSGS. Further prospective data may demonstrate the efficacy of MMF in GN.
Rubio, E; Acevedo, M
A 68-year-old male with macroscopic hematuria and constitutional symptoms as fever and weight loss. There was nothing interesting in the anamnesis or in the physical exploration. The laboratory test had an elevation of creatinine of 4 mg/dL and ten days before it had been 1.4 mg/dL. In the urine analysis: proteinuria of 1.5 G/24 h, and hematuria. On the second day we made a renal biopsy where we could seen segmental glomerular necrosis and crescent fromation in 80% of the glomeruli. In the immune study c-ANCA anti-PR3 was positive. In the complementary studies we didn't find other organs affected. With the diagnosis of pauci-immune glomerulonephritis limited to the kidney we began treatment with corticosteroids and cyclophosphamide. As the renal function was severely affected the patient needed one dialysis session. We began with 1 g intravenous methylprednisolone daily for 3 days followed by oral prednisone 60 mg daily tapering to 10 mg daily by 3 months. This was combined with 150 mg oral cyclophosphamide daily. Seven plasma exchanges were performed. At the beginning of treatment creatinine was 7 mg/dL, it was decreasing rapidly and three week after cretinine was 3 mg/Dl and he was asymptomatic. One year after treatment, creatinine is 1.4 mg/dL and the urine analysis is normal, C-ANCA are negative.
Kain, Renate; Exner, Markus; Brandes, Ricarda; Ziebermayr, Reinhard; Cunningham, Dawn; Alderson, Carol A; Davidovits, Agnes; Raab, Ingrid; Jahn, Renate; Ashour, Oliver; Spitzauer, Susanne; Sunder-Plassmann, Gere; Fukuda, Minoru; Klemm, Per; Rees, Andrew J; Kerjaschki, Dontscho
Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P41–49) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN. PMID:18836458
Anand, Ananya; Krishna, Gopal G; Sibley, Richard K; Kambham, Neeraja
We report the case of a 53-year-old woman with Sjögren syndrome and cryoglobulinemia. The patient presented with nephrotic syndrome, hematuria, and reduced estimated glomerular filtration rate. The kidney biopsy revealed diffuse endocapillary proliferation and leukocyte exudation with focal intraluminal hyaline thrombi, prominent tubulointerstitial inflammation, and vasculitis. Diffuse granular mesangial and segmental to global capillary wall staining was observed on immunofluorescence with antisera to C3 and immunoglobulin M (IgM), with less intense staining indicative of IgG and κ and λ light chains. A biopsy diagnosis of Sjögren syndrome-related cryoglobulinemic membranoproliferative glomerulonephritis and vasculitis was rendered. Subsequent investigations revealed the presence of circulating type II cryoglobulins with cryocrit of 9%. Although rare, Sjögren syndrome is the most common cause of non-hepatitis C virus-related mixed cryoglobulinemia. We discuss the possible pathogenic mechanisms involved in the development of mixed cryoglobulinemia and its evolution to lymphoma, as best described in the setting of hepatitis C virus infection. Although the specific antigen involved is unknown, it is likely that the mixed cryoglobulinemia in Sjögren syndrome is triggered by the long-term B-cell stimulation, resulting in clonal proliferation of B cells. Additional chromosomal aberrations and cytokine milieu alterations, as seen in hepatitis C virus infection, may result in prolonged B-cell survival and progression to non-Hodgkin lymphoma. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Yokoyama, Hitoshi; Okuyama, Hiroshi; Yamaya, Hideki
Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial variation in severity and manifestations. The current classification (ISN/RPS 2003) has been improved successfully for the categorization of lupus glomerulonephritis (LGN). On the basis of this classification, 480 Japanese cases revealed the following distribution: class I 3%, class II 16%, class III 13%, class IV-S 11%, class IV-G 41%, class V 16%, and class VI 1%. Class IV-G with chronicity tended to have the worst renal outcome. Nephrotic syndrome was a more frequent complication in class IV-S (50%), class IV-G (72%), and class V (56%), with poor renal and actuarial outcomes. With regard to therapy, treatment options including glucocorticoids alone or combined with antimetabolites (azathioprine, mizoribine, mycophenolate mofetil), calcineurin inhibitors (cyclosporine A, tacrolimus), or alkylating agents (intravenous cyclophosphamide injection) improved the outcome of LGN; however, there is no high-grade clinical evidence from Japan. Further studies are needed to resolve the clinicopathological problems of LGN, especially IV-S, IV-G, and pure membranous lupus nephritis in Japanese patients.
Sahutoglu, T; Atay, K; Caliskan, Y; Kara, E; Yazici, H; Turkmen, A
Amyloid A (AA) amyloidosis is a multisystemic, progressive, and severe disease. Renal involvement is a prominent feature of the disease, and the outcome of patients on dialysis is poor. We aimed to analyze the outcomes of kidney transplantation in patients with AA amyloidosis in comparison with chronic glomerulonephritis (CGN). Charts of patients who underwent kidney transplantation between 1988 and 2012 were reviewed; 41 patients with AA amyloidosis were identified, and 41 age- and sex-matched control patients with chronic CGN were included. Baseline characteristics, immunosuppressive regimens, and transplantation-related outcomes were retrieved using a standardized form. The mean follow-up period was 70.9 ± 44.9 months. The 10-year patient survival was found to be significantly worse in the AA amyloidosis group (62.5%) compared to CGN group (100%) (P = .008). During the follow-up period, three of the 41 patients (9.7%) died of sepsis and one patient died of cardiac complications in the amyloidosis group, whereas there was no patients were lost in the CGN group. The first-year, fifth-year, and tenth-year mean graft survival rates, acute and chronic rejections, and mean creatinine levels at last visits were not significantly different between the groups. Proteinuria >1 g/d, cytomegalovirus and tuberculosis infections, and rhabdomyolysis were recorded at a significantly higher rate in patients with amyloidosis. As compared to patients with CGN, patients with AA amyloidosis had a lower patient survival; equal graft survival and rejection rates; and higher risks of developing proteinuria, cytomegalovirus and tuberculosis infections, and rhabdomyolysis. Copyright © 2016 Elsevier Inc. All rights reserved.
Varshavskiĭ, V A; Sorokina, M N; Tomlina, N A; Kupriianova, L A
The article deals with the results of a clinico-functional-morphological study of the kidneys in glomerulonephritis (50 observations) which was carried out with the use of the method of puncture biopsy of the kidneys. It was shown that clinical forms of glomerulonephritis, accompanied with hematuria, were characterized by the absence of fixation of immune complexes in the basal membrane of the glomeruli. According to the electron microscopy data, this corresponds to the dissappearance of deposits from the subendothelial parts of the basal membrane. The extramembranous glomerulonephritis, revealed with the help of electron microscopy technique, was characterized by the nephrotic syndrome. An increased tension of immunological processes in the glomeruli was accompanied by a more grave clinical course of glomerulonephritis, by impairment of not only glomerulous but tubular functions as well. A greater dicrease in the function of osmotic concentration of the urine in fibroplastic types of glomerulonephritis, as compared with non-firboplastic ones, was apparently connected not only with lesiones of tubules but rather with more expressed sclerotic changes in the interstitial tissue of the kidney.
Brown, Michael C.; Smith, Rex Neal; Badhwar, Anshul K.; Parente, Oscar; Chung, Hyun chul; O’Dell, Donna; Bunch; McGregor, JulieAnne G.; Hogan, Susan L.; Hu, Yichun; Yang, Jia-Jin; Berg, Elisabeth A.; Niles, John; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.
Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti–LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti–LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti–LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti–proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti–LAMP-2 titers, respectively. There was no correlation between anti–LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti–LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti–LAMP-2 antibodies and ANCA glomerulonephritis. PMID:22021709
Iodice, Carmela; Balletta, Mario M; Minutolo, Roberto; Giannattasio, Paolo; Tuccillo, Stefano; Bellizzi, Vincenzo; D'Amora, Maurizio; Rinaldi, Giorgio; Signoriello, Giuseppe; Conte, Giuseppe; De Nicola, Luca
Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined. We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone. Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.
Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.
Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575
Jiménez, Angeles; Sánchez, Belén; Pérez Alenza, Dolores; García, Pilar; López, Jose Vicente; Rodriguez, Alejandro; Muñoz, Alvaro; Martínez, Fernando; Vargas, Astrid; Peña, Laura
The Iberian lynx is the most endangered felid species in the world, confined nowadays to two isolated metapopulations in the southwest of Spain, where less than 200 individuals survive. Little is known about the diseases that affect these animals in the wild or in captivity. Kidney samples from necropsies of 27 Iberian lynxes, wild and captive, were examined by histopathology, immunohistochemistry (IgG, IgM, IgA, laminin, type IV collagen, and fibronectin), electron microscopy (n=8) and immunogold labelling for IgM, IgG and IgA in one case, in order to characterize the glomerulopathy prevalent in this species. Urinalyses from records were available for 9 of the necropsied animals and blood and urine samples from 23 free ranging and captive Iberian lynxes were prospectively obtained in order to evaluate the renal function of the living population. A focal, diffuse membranous glomerulonephritis (MGN) that progressed with age was diagnosed in all but one of the animals in different stages not associated to concurrently known infectious diseases. Positive immunoexpression of IgM and IgG was observed in the glomerular capillary basement membranes and intramembranous electron-dense deposits, compatible with immune complexes (ICs) were seen with electron microscopy. The immunogold labelling was also positive for IgM and IgG in the electron-dense areas. The serum biochemistry and urinalyses also revealed signs of mild chronic kidney disease in 16 of the 23 animals evaluated. In conclusion, the membranous glomerulopathy affecting the Iberian lynx is a progressive disease of immune origin. We postulate a possible genetic predisposition towards the disease, enhanced by inbreeding and a possible connection to an immune-mediated systemic disease.
Hebert, L.A.; Cosio, F.G.; Birmingham, D.J.; Mahan, J.D.; Sharma, H.M.; Smead, W.L.; Goel, R. )
This study was undertaken to develop a model of immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate that could be used in subsequent studies to examine critically the role of the erythrocyte complement receptor (E-CR) in the pathogenesis of IC-mediated disease. Cynomolgus monkeys were chosen for study because they constitutively express E-CR levels that are either less than, equal to, or greater than that seen in normal man. After immunization with bovine gamma globulin (BGG), the GN induction protocol was begun in 10 cynomolgus by initiating daily i.v. administration of BGG in amounts sufficient to achieve or exceed antigen/antibody equivalence (assessed by the quantitative precipitin assay) for precipitating antibody present in the plasma volume. We found that within eight weeks of daily BGG administration of all the cynomolgus developed IC-mediated GN, irrespective of the initial E-CR level of the animals. However, the high E-CR cynomolgus tended to receive the higher BGG doses because of higher initial antibody levels to BGG. When the total number of glomerular deposits (determined by morphometric studies) per total BGG dose for each animal was plotted against the initial CR/E of that animal, there was a tendency for the animals with higher CR/E levels to have a lower number of glomerular deposits/BGG dose. Also, the total number of glomerular deposits correlated with the severity of the GN. During the early weeks of the GN induction protocol, the IC that formed in vivo (assessed by infusion of 125I-BGG) bound in large amounts to the circulating erythrocytes of the cynomolgus with medium or high E-CR levels. However, when tested after the onset of heavy proteinuria, which occurred between weeks 5 and 8 of daily BGG administration, the IC that formed in the circulation bound only poorly to circulating erythrocytes.
Grotz, W; Wanner, C; Keller, E; Böhler, J; Peter, H H; Rohrbach, R; Schollmeyer, P
Fourteen patients with Wegener's granulomatosis (WG) and severe renal and extrarenal involvement were studied (serum creatinine on admission 5.8 +/- 3.4 mg/dl). Renal histology showed a necrotizing, crescentic glomerulonephritis in all patients. Despite advanced renal disease on admission cyclophosphamide, steroids (in 13 patients) and plasma exchange (in 9 patients) caused a rapid and sustained improvement of renal function. Four patients required intermittent hemodialysis over a period of one week. After 2 weeks of treatment serum creatinine values below 2 mg/dl (n = 4) indicated a nearly complete recovery of renal function in the long-term follow up (mean serum creatinine achieved after 12 months therapy: 1.1 +/- 0.1 mg/dl (n = 4). Therefore serum creatinine values observed after 2 weeks of therapy, appear to be of prognostic value with regard to renal outcome. No relapse of active WG or progressive renal deterioration was observed during follow-up (22 +/- 13 months) except in one patient with persisting renal impairment. Three patients died (staphylococcus sepsis, intracerebral hemorrhage during hypertensive crisis, pulmonary embolism) during the first two months of therapy. The decline of serum creatinine seemed to be a better indicator of successful therapy than the decrease of anticytoplasmatic antibody (ANCA), erythrocyte sedimentation rate (ESR) and hematuria. On admission ANCA titer neither correlated with serum creatinine, the degree of renal involvement, nor was it of prognostic value. ANCA, serum creatinine and hematuria normalized within 2 to 8 months, whereas ESR and proteinuria remained elevated. Our data indicate a good prognosis of WG even with advanced renal involvement and generalized vasculitis provided aggressive treatment is performed early.
van der Woude, F J; Hoedemaeker, P J; van der Giessen, M; de Graeff, P A; de Monchy, J; The, T H; van der Hem, G K
Circulating immune complexes after a test meal were measured with three methods (PEG precipitation, Clq-ELISA and the indirect granulocyte phagocytosis test) in 10 controls, two symptomless persons with selective IgA deficiency and 14 patients with various types of glomerulonephritis, of which two patients (with idiopathic membranous glomerulopathy and local focal glomerulonephritis) also had selective IgA deficiency. The PEG and Clq-ELISA test did not show significant differences between the groups. In the two symptomless persons with selective IgA deficiency and in the patient with local focal glomerulonephritis and selective IgA deficiency the indirect granulocyte phagocytosis test (IGFT) showed a reproducible increase in IgG, IgM and complement containing immune complexes. In the last patient multiple food antigens were probably responsible for this phenomenon, a rapid amelioration of kidney function could be induced three times by giving an antigen free diet. PMID:6851247
Alexander, Jessy J; Chaves, Lee D; Chang, Anthony; Jacob, Alexander; Ritchie, Maria; Quigg, Richard J
In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex–mediated glomerulonephritis in CfH−/− mice chimeric for wild-type, CfH−/−, CD11b−/−, or FcRγ−/− bone marrow stem cells. Glomerulonephritis was worse in CD11b−/− chimeras compared with all others, whereas disease in FcRγ−/− and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b−/− chimeras had significantly more M1 macrophages and CD4+ T cells. The renal dendritic cell populations originating from bone marrow–derived CD11c+ cells were similar in all experimental groups. CD11b+ cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b−/− chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex–mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4+ T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney. PMID:25565310
Kuhn, M; Gartmann, J; Grob, P J; Widder, W; Hartmann, G
While Goodpasture syndrome was previously defined purely clinically by the combination of pneumorrhagia and glomerulonephritis, today the following immunologic criteria must also be satisfied: evidence, provided by immunofluorescent investigation of the kidneys and lungs, of antibasement membrane antibodies in the serum and linear deposits of immunoglobulins, due to direct apposition of antibasement membrane antibodies. Cases where the lesions are caused by immune complexes should no longer be designated as Goodpasture syndrome. In the light of one of our own cases of immune complex glomerulonephritis with pneumorrhagia, the question is raised whether this subdivision by means of immunologic investigations is meaningful for the clinician.
Glomerulonephritis (GN) characterized by immune complex deposits typical of postinfectious GN but with a paucity or absence of overt clinical symptoms and/or urinary abnormalities may occur after a group A streptococcus infection. The overall incidence of this type of subclinical GN is not known. To address this question, electron microscopy findings in 1012 consecutive renal biopsy specimens (952 native kidney, 60 transplant) examined by a single renal pathologist from August 1999 to April 2002 were retrospectively reviewed for the presence of distinct subepithelial and intramembranous deposits indicative of postinfectious GN. Such deposits were noted in 83 biopsy specimens, including 26 with a primary diagnosis of postinfectious GN (acute, persistent, or latent) and 57 in which these deposits were an incidental finding. In each of the latter 57 cases, some or all of the deposits showed partial or extensive loss of electron density typical of partially or largely resorbed deposits. A diagnosis of incidental postinfectious GN was not made in any biopsy specimen exhibiting another immune complex-related glomerular disease that could possibly account for the deposits, composing 443 of the 1012 biopsy specimens examined. Thirty of the 57 biopsy specimens with incidental postinfectious GN showed mesangial hypercellularity, although this was focal and segmental in all but 3 cases and was not accompanied by the endocapillary hypercellularity typical of acute postinfectious lesions. Immunofluorescence microscopy revealed glomerular deposits of C3 in >90% of these biopsy specimens and IgM deposits in 66%, but only rare IgG, IgA, and Cq deposits. Twenty-three (40%) of these 57 biopsy specimens exhibited diabetic nephropathy, either alone or in combination with another lesion; for perspective, only 128 (13%) of the 1012 biopsy specimens examined showed evidence of diabetic nephropathy. In summary, incidental evidence of resolving or largely healed postinfectious GN was noted
Birmingham, D.J.; Hebert, L.A.; Cosio, F.G.; VanAman, M.E. )
Multiple lines of evidence indicate that the erythrocyte complement receptor (E-CR) system, which is unique to the primate, may play an important role in the clearing of immune complexes (ICs) from the circulation. However, all previous investigations of IC/E-CR interactions in vivo have involved the study of small amounts of preformed or passively formed ICs interacting with E-CR that were numerically in vast excess. The present study was undertaken to assess IC/E-CR interactions under conditions in which large amounts of ICs were formed in the circulation, amounts that when sustained for several weeks by daily intravenous administration of antigen resulted in the development of active glomerulonephritis. Twelve cynomolgus monkeys with E-CR levels ranging from 25 to 5000 mean CRs per erythrocyte (CR/E) were actively immunized to BGG, and 6 to 12 weeks later they were studied first at low levels of IC formation in vivo and then at high levels of IC formation in vivo (H-Protocol experiments, mean 125I-labeled BGG dose 4.9 mg/kg given over 10 minutes, a state approximating antigen-antibody equivalence). Cynomolgus monkeys with fewer than 100 CR/E showed no evidence of binding of ICs to erythrocytes with either low-dose or high-dose 125I-labeled BGG. However, cynomolgus monkeys with greater than 450 CR/E showed significant binding of ICs to erythrocytes: mean peak binding of 125I-labeled BGG to erythrocytes was 22.1% +/- 1.1% in the L-Protocol experiments and 33.4% +/- 8.0% in the H-Protocol experiments. During H-Protocol experiments, mean CR/E, measured by using a monoclonal anti-human CR1 antibody, decreased acutely, with recovery of E-CR levels within the next 24 to 72 hours. The acute decrease in E-CR levels could not be accounted for by occupancy of E-CR by ICs or by change in hematocrit.
Shimizu, Maki; Sekiguchi, Takanori; Kishi, Natsuko; Goji, Aya; Takahashi, Tomoko; Kozan, Hiroko; Sakaguchi, Zenichi; Kinoshita, Yukiko; Matsuura, Sato; Suga, Kenichi; Urushihara, Maki; Kondo, Shuji; Kagami, Shoji; Ohara, Katsuaki
A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.
Lovett, D. H.; Johnson, R. J.; Marti, H. P.; Martin, J.; Davies, M.; Couser, W. G.
Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury. Images Figure 2 Figure 3 Figure 5 Figure 4 Figure 6 Figure 7 Figure 8 and Figure 9 Figure 10 Figure 11 Figure 12 PMID:1321565
Prabhu, Chaitanya; Arulneyam, Jayanthi; Remalayam, Bhavith; Adil, Mohammed
We report a 58-year-old man with multiple yellow jacket stings who developed urticaria, renal failure, quadriparesis, rhabdomyolysis in succession. Investigations revealed renal and hepatic dysfunction, proteinuria, demyelinating polyradiculoneuropathy, acute tubular necrosis and glomerulonephritis. He improved with methylprednisolone, antihypertensives and two sessions of haemodialysis. PMID:25984147
Viswanathan, Stalin; Prabhu, Chaitanya; Arulneyam, Jayanthi; Remalayam, Bhavith; Adil, Mohammed
We report a 58-year-old man with multiple yellow jacket stings who developed urticaria, renal failure, quadriparesis, rhabdomyolysis in succession. Investigations revealed renal and hepatic dysfunction, proteinuria, demyelinating polyradiculoneuropathy, acute tubular necrosis and glomerulonephritis. He improved with methylprednisolone, antihypertensives and two sessions of haemodialysis.
OʼShaughnessy, Michelle M; Liu, Sai; Montez-Rath, Maria E; Lafayette, Richard A; Winkelmayer, Wolfgang C
Whether kidney transplantation rates differ by glomerulonephritis (GN) subtype remains largely unknown. Using the US Renal Data System, we identified all adult patients with end-stage renal disease attributed to 1 of 6 GN subtypes who initiated dialysis in the US (1996-2013). Patients with diabetic nephropathy (DN) and autosomal-dominant polycystic kidney disease (ADPKD) served as "external" non-GN comparators. Using Cox proportional hazards regression, with death considered a competing risk, we estimated hazard ratios (HRs) (95% confidence intervals [CI]) for first kidney transplantation, controlling for year, demographics, comorbidities, socioeconomic factors, and Organ Procurement Organization. Among 718 480 patients studied, unadjusted and multivariable-adjusted transplant rates differed considerably across GN subtypes. Adjusted transplant rates were highest for patients with IgA nephropathy (IgAN) (referent) and lower for all other groups: focal segmental glomerulosclerosis (HR, 0.80; 95% CI, 0.77-0.82), membranous nephropathy (HR, 0.88; 95% CI, 0.83-0.93), membranoproliferative GN (HR, 0.84; 95% CI, 0.76-0.92), lupus nephritis (HR, 0.69; 95% CI, 0.66-0.71), vasculitis (HR, 0.66; 95% CI, 0.61-0.70), DN (HR, 0.50; 95% CI, 0.47-0.52), ADPKD (HR, 0.85; 95% CI, 0.82-0.88). Reduced kidney transplantation rates among comparator groups were driven more so by lower rates of waitlisting (HRs vs IgAN, ranged from 0.49 for DN to 0.92 for membranous nephropathy or ADPKD) than by lower rates of deceased donor kidney transplantation after waitlisting (rates were only significantly lower, vs IgAN, for those with secondary GN subtypes: lupus nephritis [HR,0.91; 95% CI, 0.86-0.97], vasculitis [HR, 0.85; 95% CI, 0.76-0.94), DN [HR, 0.73; 95% CI, 0.69-0.77]). Identifying underlying reasons for apparent disease-specific barriers to kidney transplantation might inform center-specific transplant candidate selection procedures, along with national organ allocation policies, leading
Schwartz, Melvin M; Korbet, Stephen M; Lewis, Edmund J
The International Society of Nephrology/ Renal Pathology Society classification (ISN/RPS) of lupus glomerulonephritis (GN) divides diffuse GN (>/=50% involvement) into diffuse segmental (IV-S) and diffuse global GN (IV-G). This division tests whether the pathogenesis and clinical outcomes are the same as when similar patients are classified using the World Health Organization (WHO) classification into severe segmental (WHO III >/=50%) and diffuse global (WHO-IV) GN. Thirty-nine renal biopsies with WHO class IV and 44 with WHO III >/= 50% were reclassified using the ISN/RPS and were correlated with pathogenesis and outcome. There were 22 biopsies with ISN/RPS class IV-S. ISN/RPS class IV-G comprises two morphologically discrete classes of renal biopsies: 39 biopsies originally classified as WHO class IV (WHO-IV) and 22 that switched from WHO III >/=50% to ISN/RPS class IV-G (IV-Q). We will analyze IV-S, IV-Q and WHO-IV separately. WHO-IV had significantly more immune aggregate deposition than IV-S and IV-Q. WHO-IV had lower serum complements C3 (P = 0.05) and C4 (P = 0.05) than patients with IV-Q. Patients with WHO-IV had more remissions (56%) than IV-Q (23%) (P = 0.01), and stable renal function at the last follow-up was less frequent in patients with IV-Q (18%) than IV-S (50%, P = 0.05) and WHO-IV (62%, P = 0.001). Renal survival and renal survival without end-stage renal disease were different when the patients were diagnosed as WHO classes III >/=50% and IV, but the outcomes for ISN/RPS class IV-S and IV-G (WHO-IV plus IV-Q) were not different. WHO III >/=50% and WHO-IV lupus GN are not congruent with ISN/RPS IV-S and IV-G. The ISN/RPS minimizes pathological and outcome differences between classes IV-S and IV-G which results in the loss of informational content from the renal biopsies. ISN/RPS does not detect pathogenetic or clinical differences among patients with severe lupus GN.
Milošević, Danko; Husar, Karmela; Batinić, Danica; Ćorić, Marijana; Jović, Anamaria; Turudić, Daniel; Pelajić, Stipe; Dumić Čule, Ivo
Generalized psoriasis and renal function disorder were previously described in sporadic adult cases, revealing a new entity - psoriatic nephropathy. So far there have been only two cases describing this association in children. We present and discuss a case of 10-year-old girl with the unique biopsy findings of double glomerulonephritis associated with the simultaneous onset of generalized psoriasis.
Zufarova, Sh A
The investigations performed showed that pregnant women with chronic pyelonephritis (CP) and chronic glomerulonephritis (CG) have certain response to therapy done in accordance with level of kidney function activity. In the pregnant women with CP and CG and kidney functional reserve KFR > 10% and from 5 to 10% the treatment efficacy was higher and practically absent in pregnant women with KFR < 5%.
Zufarova, Sh A
Pregnant women with pyelonephritis (PN) and glomerulonephritis (GN) were shown to have response to the therapy in accordance with level of kidney functional activity. The women with PN and GN have the treatment efficacy higher with Kidney Functional Reserve KFR > 10% and from 5 to 10% and practically absent in pregnant women with KFR < 5% (Kidney functional reserve).
McGuire, Brendan M; Julian, Bruce A; Bynon, J Steve; Cook, William J; King, Steven J; Curtis, John J; Accortt, Neil A; Eckhoff, Devin E
Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. To describe renal histologic characteristics and concomitant clinical features in HCV-infected patients with end-stage cirrhosis. Case series. Single-center liver transplant program in the United States. 30 patients who received liver transplants for HCV-induced cirrhosis. Kidney biopsy during liver engraftment. Clinical data and laboratory tests of renal function within 6 months before liver transplantation. Twenty-five patients had immune-complex glomerulonephritis: membranoproliferative glomerulonephritis type 1 (n = 12), IgA nephropathy (n = 7), and mesangial glomerulonephritis (n = 6). Of these patients, 10 had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For 5 others, the only renal abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. This small observational study did not include patients with nonviral cirrhosis and did not document post-transplantation outcomes. Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. Its potential to cause renal failure after liver transplantation may be underappreciated.
Raybould, Jillian E; Raybould, Alison L; Morales, Megan K; Zaheer, Misbah; Lipkowitz, Michael S; Timpone, Joseph G; Kumar, Princy N
Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti-neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.
Murray, N; Lyons, J; Chappell, M
Twenty days after a streptokinase infusion given for myocardial infarction, a patient developed a group G streptococcal throat infection. Thirteen days later he presented with a serum sickness type illness and progressive renal failure. Renal biopsy showed crescentic glomerulonephritis. Images Fig 1 Fig 2 PMID:3790385
McPhaul, J J; Mullins, J D
A prospective study was undertaken to establish the incidence of glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and its histopathological characteristics in a clinical group of patients presenting with renal disease. Biopsies from 43 of 409 consecutive patients technically satisfactory for direct immunofluorescent (IF) examination had diffuse and generalized linear localization of host immunoglobulin (Ig); two other badly scarred kidneys tested negative to IF although GBM antibodies were eluted. Confirmatory evidence of GBM antibody-mediated disease in these patients came from whole kidney or biopsy elutions (15 patients), serologic assays for circulating GBM antibodies by indirect IF (9 of 38 patients), radioimmunoassay (26 of 34), and hemagglutination (31 of 32). Although sera were not tested from six patients, circulating antibodies were demonstrated by some test in 36 of 39 of the remainder. Histologically, half of the patients had minor and nonspecific glomerular abnormalities or mild focal proliferative glomerulonephritis. More severely involved kidneys had focal necrotizing (17%), rapidly progressive (7%), and chronic, usually sclerosing, glomerulonephritis (27%). Clinical courses of these patients comparably were quite variable, ranging from indolent microhematuria and/or gross hematuric bouts to progressive renal failure; nephrotic syndrome was observed in 11 patients. GBM antibody-mediated glomerulonephritis may be a relatively mild disease with apparently stable renal function, although 16 patients have experienced functional deterioration, and 11 have progressed to dialysis, renal transplantation, or death. Images PMID:56340
Cook, H. T.; Sullivan, R.
Nitrite (NO2-) is the major end product of nitric oxide (NO) production in cell culture. The authors have examined nitrite production by glomeruli in in situ immune complex glomerulonephritis in the rat. Glomerulonephritis was induced by unilateral renal perfusion of cationized human gamma G immunoglobulin (IgG) in preimmunized rats. NO2- was measured in culture supernatants of isolated glomeruli after 48 hours. NO2- was produced by nephritic glomeruli with a maximum 4 days after induction of glomerulonephritis (24.4 +/- 11.4 pmol/glomerulus/48 hours). Production was increased by lipopolysaccharide (LPS; 1 micrograms/ml) (54 +/- 4.9 pmol/glomerulus; P less than 0.001). NO2- production was inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine demonstrating synthesis through NO. Dexamethasone (10(-7) mol/l [molar]) reduced LPS-stimulated production by peritoneal macrophages and nephritic glomeruli (P less than 0.01). Macrophages isolated from nephritic glomeruli produced NO2- (4.9 +/- 0.6 nmols/10(5) cells). The production of NO by nephritic glomeruli has implications for mechanisms of glomerular injury and glomerular hemodynamics. The effect of dexamethasone may explain in part the ameliorative effect of steroids in glomerulonephritis. Images Figure 4 PMID:1951626
Togashi, Yuko; Imura, Naoko; Miyamoto, Yohei
The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.
Zhang, Hongxia; Mao, Xing; Sun, Yu; Hu, Ruimin; Luo, Weili; Zhao, Zhonghua; Chen, Qi; Zhang, Zhigang
Podocyte injury is a pivotal factor during the progression of glomerular diseases. It has been demonstrated that the expression of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is increased in injured podocytes in a number of types of glomerulonephritis. However, its mechanism of regulation remains to be elucidated. A previous study by our group suggested that UCH-L1 is a downstream protein of nuclear factor (NF)-κB signaling. In the present study, the involvement of NF-κB in the regulation of the expression of UCH-L1 was investigated in diseased podocytes in vivo and in vitro. Increases in the expression of phosphorylated NF-κB at p65 and UCH-L1 were detected using immunohistochemical analysis of kidney biopsy tissues from 56 cases of nephritis, including immunoglobulin A nephropathy, membranous glomerulonephritis and lupus nephritis. The two indicators were also analyzed using western blot analysis in cultured murine podocytes stimulated by inflammatory factors. The results of the present study demonstrated that in human renal biopsies of several cases of immune complex-mediated glomerulonephritis, the increases of NF-κB and UCH-L1 were positively correlated with the number of diseased podocytes. By contrast, in non-immune complex-mediated glomerulonephritis, no clear activation of NF-κB and increase of UCH-L1 expression was observed. In vitro, immune stimulation also led to the upregulation of UCH-L1 through the NF-κB signaling pathway in mouse podocytes. In conclusion, the results of the present study suggested that the activation of NF-κB and upregulation of UCH-L1 in podocytes may be vital in podocyte injury associated with immune complex-mediated glomerulonephritis.
Couser, W G; Johnson, R J; Young, B A; Yeh, C G; Toth, C A; Rudolph, A R
Complement is a major mediator of tissue injury in several types of glomerulonephritis. However, no therapeutic agents that inhibit complement activation are available for human use. sCR1 (TP10, BRL 55736) is a recombinant, soluble human complement receptor 1 (CR1) molecule lacking transmembrane and cytoplasmic domains that inhibits C3 and C5 convertase activity by preferentially binding C4b and C3b. To test the efficacy of sCR1 on complement-mediated glomerulonephritis, rats were pretreated with sCR1 (60 mg/kg per day) before and during the induction of three models of complement-dependent glomerulonephritis (concanavalin A and antithymocyte serum models of proliferative glomerulonephritis, passive Heyman nephritis). Daily sCR1 and complement hemolytic activity levels were measured, and renal histology and urine protein excretion were examined. Mean serum sCR1 levels of 100 to 200 micrograms/mL were maintained with a reduction in complement hemolytic activity to less than 15% in most animals. In the antithymocyte serum model, sCR1-treated animals had significant reductions in mesangiolysis, glomerular platelet and macrophage infiltrates, and proteinuria at 48 h. In the concanavalin A model, sCR1 significantly reduced glomerular C3 and fibrin deposits, platelet infiltrates, and proteinuria at 48 h. In passive Heymann nephritis, proteinuria was also significantly reduced (199 +/- 8.5 versus 125 +/- 16 mg/day, P < 0.002) at 5 days. It was concluded that sCR1 significantly reduces both morphologic and functional consequences of several different types of complement-mediated glomerulonephritis and deserves evaluation as a potential therapeutic agent in complement-mediated immune glomerular disease in humans.
Haas, M; Jafri, J; Bartosh, S M; Karp, S L; Adler, S G; Meehan, S M
Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were
Burke, Rebecca J; Chang, Christopher
Acute rheumatic fever is an inflammatory sequela of Group A Streptococcal pharyngitis that affects multiple organ systems. The incidence of acute rheumatic fever has been declining even before the use of antibiotics became widespread, however the disease remains a significant cause of morbidity and mortality in children, particularly in developing countries and has been estimated to affect 19 per 100,000 children worldwide. Acute rheumatic fever is a clinical diagnosis, and therefore subject to the judgment of the clinician. Because of the variable presentation, the Jones criteria were first developed in 1944 to aid clinicians in the diagnosis of acute rheumatic fever. The Jones criteria have been modified throughout the years, most recently in 1992 to aid clinicians in the diagnosis of initial attacks of acute rheumatic fever and to minimize overdiagnosis of the disease. Diagnosis of acute rheumatic fever is based on the presence of documented preceding Group A Streptococcal infection, in addition to the presence of two major manifestations or one major and two minor manifestations of the Jones criteria. Without documentation of antecedent Group A Streptococcal infection, the diagnosis is much less likely except in a few rare scenarios. Carditis, polyarthritis and Sydenham's chorea are the most common major manifestations of acute rheumatic fever. However, despite the predominance of these major manifestations of acute rheumatic fever, there can be significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-Streptococcal reactive arthritis. This overlap between disease processes has led to continued investigation of the pathophysiology as well as development of new biomarkers and laboratory studies to aid in the diagnosis of acute rheumatic fever and distinction from other disease processes.
Mazur, Elżbieta; Bochyńska, Ewa; Juda, Marek; Kozioł-Montewka, Maria
Group A Streptococcus (GAS) pharyngitis is currently the only commonly occurring form of acute pharyngitis for which antibiotic therapy is definitely indicated. Polish guidelines advocate the use of modified Centor score (MCS) to assess the probability of GAS pharyngitis. They advise performing throat culture or rapid antigen detection test (RADT) in children with score 2-3 in MCS and treating with antibiotic only those in whom GAS was detected. Negative RADT results should be confirmed by culture. In children with score 4, the guidelines allow to introduce empiric antibiotic therapy. Phenoxymethyl penicillin is recommended as a drug of choice to treat GAS pharyngitis. The aim of our study was to evaluate the accuracy of strategy recommended by Polish guidelines in identifying those children with acute pharyngitis who require antibiotic treatment. Hence, diagnostic values of score 4 in MCS and RADT were assessed using throat culture as a reference standard. Phenoxymethyl penicillin efficacy in GAS eradication and prevention of post-streptococcal complications were estimated as well. Ninety children between 2 and 15 years of age with acute pharyngitis symptoms suggesting GAS etiology (MCS ≥ 2), participated in our study. At the initial visit MCS was evaluated and two throat swabs were collected to perform RADT and culture. In children with GAS pharyngitis treated with penicillin, microbiological cure was assessed by performing two control throat cultures. Next, children were under observation for 3 months. Positive predictive value of score 4 in MCS turned out to be 48.05% (95% CI: 36.5-59.7%). RADT sensitivity, specificity and diagnostic accuracy proved to be 100%, 96%, and 98%, respectively. GAS eradication rate in children treated with penicillin turned out to be 92.5%. No post-streptococcal sequelae occurred in any child in 3-month observation. Empiric antibiotic therapy in children with score 4 in MCS will result in significant overtreatment of those with
Fatima, R; Jha, R; Gowrishankar, S; Narayen, G; Rao, B S
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly recognized entity caused by monoclonal deposition of IgG. PGNMID resembles immune complex glomerulonephritis (GN) on light and electron microscopy. The monotypic immunoglobulin deposits seen on immunofluorescence (IF) clinches the diagnosis. We report a case of proliferative GN associated MGRS and review the relevant literature. The patient had significant proteinuria and elevated serum creatinine. The renal biopsy showed proliferative GN with focal crescents and monoclonal immune deposits confirming a diagnosis of PGNMID. Serum work up showed no monoclonal proteins. Proliferative GN as a manifestation of a monoclonal gammopathy needs to be borne in mind especially in renal biopsies of older patients.
Fatima, R.; Jha, R.; Gowrishankar, S.; Narayen, G.; Rao, B. S.
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly recognized entity caused by monoclonal deposition of IgG. PGNMID resembles immune complex glomerulonephritis (GN) on light and electron microscopy. The monotypic immunoglobulin deposits seen on immunofluorescence (IF) clinches the diagnosis. We report a case of proliferative GN associated MGRS and review the relevant literature. The patient had significant proteinuria and elevated serum creatinine. The renal biopsy showed proliferative GN with focal crescents and monoclonal immune deposits confirming a diagnosis of PGNMID. Serum work up showed no monoclonal proteins. Proliferative GN as a manifestation of a monoclonal gammopathy needs to be borne in mind especially in renal biopsies of older patients. PMID:25484532
Diouf, B; Diao, M; Niang, A; Ka, E F; Moreira Diop, T
Berger's disease or IgA glomerulonephritis is the most common glomerular nephropathy in Europe and represent a rare event in blacks. Here, we describe the case of a 43 years old black Senegalese whose disease was discovered while investigating a persistent proteinuria with high blood pressure and chronic renal failure, but without hematuria. We point out the uncommon feature of this clinical presentation and the importance of bad prognostic factors presented by this patient. We obtained a good outcome by means of converting enzyme inhibitors and corticosteroid therapies: regression of renal failure and normalization of blood pressure. The generalization of renal biopsy practice would lead to a better knowledge of the incidence of this disease among Senegalese people. Indeed, renal biopsy is the main tool to diagnose glomerulonephritis and subsequently adapt the therapy aimed at preventing the possible evolution to end stage renal disease.
Luna, Mariana; Bocanegra, Victoria; Vallés, Patricia G
Granulomatosis with polyangiitis (GPA) is associated with a broad range of clinical manifestations including renal disease. It is a systemic vasculitis that is rarely encountered in children. We present a 14-year-old girl who suffered from pharyngitis 1 week before admittance to hospital. She was admitted for macroscopic hematuria and oliguria, under the possibility of nephritic syndrome. Renal failure with rapidly progressive glomerulonephritis occurred within 24 hours. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and renal biopsy revealed pauci-immune crescentic focal necrotizing glomerulonephritis. Treatment including methylprednisolone and cyclophosphamide intravenous pulses allowed renal recovery after 3 weeks. The clinical, hematological, and biochemical parameters improved substantially, achieving remission. Granulomatosis with polyangiitis, although rare in children, should be considered in the above clinical scenario. This case underlines that knowledge of renal histology diagnosis and early aggressive immunosuppressive therapy are essential for the management of these patients. PMID:24790466
Howell, David N
Kidney biopsy is a mainstay in the diagnosis and management of renal disease in patients with systemic lupus erythematosus. Though biopsies from patients with lupus typically show various forms of immune complex glomerulonephritis, other pathologies are occasionally encountered, including unusual lupus-related nephropathies, other forms of autoimmune disease, and occasional renal disorders without any direct connection with lupus or autoimmunity. Electron microscopy is a powerful tool for detecting and classifying these unusual conditions, which frequently have important therapeutic and prognostic implications.
Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang
Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.
Ma, Frank Y.; Han, Yingjie; Nikolic-Paterson, David J.; Kolkhof, Peter; Tesch, Greg H.
Background/Aim Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Methods Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Results Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). Conclusions The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases. PMID:26700873
Behmoaras, Jacques; Bhangal, Gurjeet; Smith, Jennifer; McDonald, Kylie; Mutch, Brenda; Lai, Ping Chin; Domin, Jan; Game, Laurence; Salama, Alan; Foxwell, Brian M; Pusey, Charles D; Cook, H Terence; Aitman, Timothy J
Crescentic glomerulonephritis is an important cause of human kidney failure for which the underlying molecular basis is largely unknown. In previous studies, we mapped several susceptibility loci, Crgn1–Crgn7, for crescentic glomerulonephritis in the Wistar Kyoto (WKY) rat1. Here we show by combined congenic, linkage and microarray studies that the activator protein-1 (AP-1) transcription factor JunD is a major determinant of macrophage activity and is associated with glomerulonephritis susceptibility. Introgression of Crgn2 from the nonsusceptible Lewis strain onto the WKY background leads to significant reductions in crescent formation, macrophage infiltration, Fc receptor–mediated macrophage activation and cytokine production. Haplotype analysis restricted the Crgn2 linkage interval to a 430-kb interval containing Jund, which is markedly overexpressed in WKY macrophages and glomeruli. Jund knockdown in rat and human primary macrophages led to significantly reduced macrophage activity and cytokine secretion, indicating conservation of JunD function in macrophage activation in rats and humans and suggesting in vivo inhibition of Jund as a possible new therapeutic strategy for diseases characterized by inflammation and macrophage activation. PMID:18443593
Schulze, M.; Pruchno, C. J.; Burns, M.; Baker, P. J.; Johnson, R. J.; Couser, W. G.
In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation. Images Figure 1 Figure 2 Figure 3 PMID:7678717
Turner, Jan-Eric; Paust, Hans-Joachim; Steinmetz, Oliver M.; Peters, Anett; Riedel, Jan-Hendrik; Erhardt, Annette; Wegscheid, Claudia; Velden, Joachim; Fehr, Susanne; Mittrücker, Hans-Willi; Tiegs, Gisa; Stahl, Rolf A.K.
T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17–producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNγ-producing Th1 cells are CCR6−. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6−/− mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis. PMID:20299360
Chaudhry, A R; Chaudhry, M R; Papadimitriou, J C; Drachenberg, C B
Bartonella henselae (BH) is the main cause of cat scratch disease (CSD), which more typically presents as a self-limited localized suppurative lymphadenopathy in immunocompetent individuals. In contrast, immunocompromised patients commonly have systemic disease with life-threatening complications. In addition to the angioproliferative lesions, such as bacillary angiomatosis, an increasing number of immune post-infectious complications are being recognized with BH infections, including glomerulonephritis, vasculitis, hemophagocytic syndrome, and neurological problems. We report the case of a renal transplant recipient who developed CSD in the second year post transplantation. In addition to prolonged fever and generalized lymphadenopathy and splenomegaly requiring differentiation from a post-transplant lymphoproliferative disorder, the course was complicated by the development of dermal leukocytoclastic vasculitis and pauci-immune necrotizing and crescentic glomerulonephritis, which led to failure of the renal graft. Glomerulonephritis as a complication of CSD has never been described in a kidney allograft, to our knowledge. Awareness of the diverse clinical symptoms associated with BH, including granulomatous/suppurative lesions and other less common complications can lead to more rapid and accurate diagnosis. Also, as recommended by the current guidelines, a thorough history of pet ownership should be part of the clinical evaluation before and after transplantation for all transplant recipients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Ostalska-Nowicka, Danuta; Malinska, Agnieszka; Silska, Magdalena; Perek, Bartlomiej; Zachwieja, Jacek
Introduction The aim of our study was to analyse the efficacy and safety of mycophenolate mofetil (MMF) as part of the complex immunosuppressive therapy in children with different types of primary and secondary glomerulonephritis, who were not eligible for the standard treatment routine suggested by evidence-based guidelines. Material and methods The study group comprised 85 children with proteinuric glomerulopathies hospitalized between 2007 and 2010, who were non-responders to immunosuppressive therapy. The dose of MMF was established as 1 g/m2/24 h. Remission was defined as negative proteinuria in three consecutive urinalyses. Results The patients were divided into 4 groups: idiopathic nephrotic syndrome (n = 35), primary glomerulonephritis (n = 15), auto-antibody associated glomerulonephritis (n = 20) and lupus nephropathy (LN, n = 15). Ten patients from the first group (29%) and 5 patients each from the second and third group (34% and 25% respectively) did not respond to MMF therapy. On the other hand, all the children diagnosed with LN have reached clinical and biochemical remission. Conclusions Alternative rescue MMF therapy should always be taken into consideration in proteinuric patients who are non-responders to steroids, cyclosporine A and cyclophosphamide in whom the initial glomerular filtration rate is higher than 60 ml/min/1.73m2. It is recommended that MMF be administered as part of the standard treatment regimen in patients diagnosed with lupus nephropathy. In these groups of patients, the potent benefits of this therapy are higher than expected side-effects. PMID:22328889
Ostalska-Nowicka, Danuta; Malinska, Agnieszka; Silska, Magdalena; Perek, Bartlomiej; Zachwieja, Jacek; Nowicki, Michal
The aim of our study was to analyse the efficacy and safety of mycophenolate mofetil (MMF) as part of the complex immunosuppressive therapy in children with different types of primary and secondary glomerulonephritis, who were not eligible for the standard treatment routine suggested by evidence-based guidelines. The study group comprised 85 children with proteinuric glomerulopathies hospitalized between 2007 and 2010, who were non-responders to immunosuppressive therapy. The dose of MMF was established as 1 g/m(2)/24 h. Remission was defined as negative proteinuria in three consecutive urinalyses. The patients were divided into 4 groups: idiopathic nephrotic syndrome (n = 35), primary glomerulonephritis (n = 15), auto-antibody associated glomerulonephritis (n = 20) and lupus nephropathy (LN, n = 15). Ten patients from the first group (29%) and 5 patients each from the second and third group (34% and 25% respectively) did not respond to MMF therapy. On the other hand, all the children diagnosed with LN have reached clinical and biochemical remission. Alternative rescue MMF therapy should always be taken into consideration in proteinuric patients who are non-responders to steroids, cyclosporine A and cyclophosphamide in whom the initial glomerular filtration rate is higher than 60 ml/min/1.73m(2). It is recommended that MMF be administered as part of the standard treatment regimen in patients diagnosed with lupus nephropathy. In these groups of patients, the potent benefits of this therapy are higher than expected side-effects.
Gan, Poh-Yi; O’Sullivan, Kim M.; Ooi, Joshua D.; Alikhan, Maliha A.; Odobasic, Dragana; Summers, Shaun A.; Kitching, A. Richard
Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4+ effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID:26374606
Aoki, Yoshihiro; Tanimoto, Izumi; Miyauchi, Yoshihiro; Suzuki, Yoshio; Shiojiri, Toshiaki
Patient: Female, 44 Final Diagnosis: Anti-glomerular basement membrane glomerulonephritis Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Type 1 diabetes mellitus (DM) tends to complicate other autoimmune diseases. When considering renal dysfunction in patients with DM, diabetic nephropathy is a likely diagnosis. By contrast, anti-glomerular basement membrane (GBM) glomerulonephritis, an autoimmune disease, is one cause of rapidly progressive glomerulonephritis. Case Report: We report the case of a 44-year-old woman diagnosed with anti-glomerular basement membrane (GBM) glomerulonephritis. The diagnosis was made on the basis of serological test results and pathological findings of a renal biopsy. Five years before admission, she was diagnosed with type 1 DM. At admission, she presented with a fever, chills, nausea, low back pain, and malaise, which were followed by progressive renal dysfunction. The initial presentation mimicked a urinary tract infection, which delayed the correct diagnosis. Conclusions: Our patient’s course strongly suggests that rapidly progressive glomerulonephritis should be considered as an early differential diagnosis in cases of progressive renal dysfunction, especially when accompanied by fever, regardless of the underlying disease. PMID:28344312
Miyata, Naoko; Kobayashi, Tomoko; Matsukawa, Yoshihiro; Sawada, Shigemasa; Nishinarita, Susumu; Horie, Takashi
We report two patients with scleroderma, 73-year-old female and 67-year-old female, who developed anti neutrophil cytoplasmic autoantibody (ANCA) associated rapid progressive glomerulonephritis (RPGN). Both patients have had a long history of scleroderma (23 and 14 years, respectively) when ANCA-associated glomerulonephritis occurred. In the first patient, scleroderma was localized in both fingers. She has been followed-up as CREST syndrome rather than systemic sclerosis. The complaints on admission were leg edema and left chest pain in the first patient, and a pyrexia and dyspnea in the second patient. Both patients showed pulmonary manifestation (pleural effusion in the first patient, interstitial pneumonia and alveolar hemorrhage in the second patient, respectively) and rapid progressive glomerulonephritis. Both patients died in spite of corticosteroid therapy. Autopsy findings in the second patient demonstrated crescentic glomerulonephritis and alveolar hemorrhage. Our cases demonstrated that MPO-ANCA associated glomerulonephritis could be associated with limited scleroderma as well as systemic scleroderma. In these condition, the prognosis will be poor if scleroderma seemed to be stable.
Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the
Wehrmann, M; Bohle, A; Bogenschütz, O; Eissele, R; Freislederer, A; Ohlschlegel, C; Schumm, G; Batz, C; Gärtner, H V
A retrospective long-term study (average follow-up time 5.2 years) of 334 patients with idiopathic membranous glomerulonephritis (MGN) was carried out with the following results: 1) MGN was found to have a relatively good prognosis when all cases were considered together: 5-year kidney survival rate (KSR) -88%, and 10-year KSR -77%. 2) Univariate survivorship analysis showed the following morphological and clinical parameters to be associated with an increased risk of terminal renal insufficiency or death from renal disease: a) tubulo-interstitial changes; b) glomerular stage III as opposed to stages I and II; c) elevation of serum creatinine concentration at the time of the biopsy; d) arterial hypertension at the time of the biopsy. 3) Multivariate analysis showed that only tubulo-interstitial changes (interstitial fibrosis and/or acute renal failure) found at the time of the biopsy and their clinical correlate, serum creatinine concentration, were significant and therefore of definite prognostic importance. 4) Unsystematic therapy with steroids and/or cytostatic agents does not improve the long-term prognosis of MGN. 5) The cause of disease in the tubulo-interstitial system in MGN is discussed. Interstitial fibrosis is considered to develop possibly as a consequence of unresorbed interstitial edema which can develop during an episode of acute renal failure. Coexisting T-cell-mediated disease in the region of the intertubular capillaries is also considered as a possible factor in the development of interstitial fibrosis.
Ayli, Deniz; Gonul, Ipek; Yuksel, Osman; Ozturk, Ramazan; Yildiz, Ayla; Yenigun, Ezgi; Piskinpasa, Serhan; Turgut, Didem; Koc, Eyup; Odabas, Ali Riza
Introduction Glomerulonephritis is still the primary cause among the diseases causing end stage renal disease. Helicobacter pylori (HP), also having a local proinflammatory effect on gastric mucosa, can trigger a local and systemic inflammatory response, and consequently have a role in the development of extragastrointestinal defects. Material and methods The study was composed of patients diagnosed with primary glomerulonephritis who had dyspeptic complaints throughout the diagnosis. Patients who received endoscopic biopsy upon the determination of pathologic findings in their upper gastrointestinal endoscopy were HP positive in their biopsy material. A triple eradication therapy was initiated for HP. Results The study included 14 female and 19 male patients, 33 in total, whose biopsy material was determined to be HP positive. Before the eradication for HP, we found serum albumin to be 34.0 (19.0–51.0) g/l, serum total protein 58.6 ±12.9 g/l, serum creatinine 0.9 (0.5–1.2) and proteinuria 3069 (652–12392) mg/day in 24-hour urine. After the eradication, however, serum albumin was found to be 40 (20–52) g/l, serum total protein 62.3 ±11.1 g/l, serum creatinine 1.02 (0.6–1.29) mg/dl and proteinuria was 2850 (172–15181) mg/day in 24-hour urine. A comparison of the results showed that a statistically significant difference is established between the serum albumin, total protein and creatinine values (p = 0.001, p = 0.001 and p = 0.021, respectively), but not between proteinuria values in 24-hour urine (p = 0.990). Conclusions Patients with primary glomerulonephritis, HP eradication treatment has an effect on serum albumin levels. PMID:26322088
Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J
Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh−/−) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19+ B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness. PMID:23347386
Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J
Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh(-/-)) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19(+) B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.
Luque, Yosu; Cathelin, Dominique; Vandermeersch, Sophie; Xu, Xiaoli; Sohier, Julie; Placier, Sandrine; Xu-Dubois, Yi-Chun; Louis, Kevin; Hertig, Alexandre; Bories, Jean-Christophe; Vasseur, Florence; Campagne, Fabien; Di Santo, James P; Vosshenrich, Christian; Rondeau, Eric; Mesnard, Laurent
Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells. The Rag2(-/-)Il2rg(-/-) or Rag2(-/-)Il2rb(-/-) mice harbor an additional deletion of either the common gamma chain (γC) or the interleukin-2 receptor β subunit (IL-2Rβ), respectively, impairing IL-15 signaling in particular. As expected, all these strains developed severe anti-GBM-GN. Additionally, bone marrow replenishment experiments allowed us to deduce a protective role for the glomerular-expressed γC during anti-GBM-GN. Given that IL-15 has been found highly expressed in nephritic kidneys despite the absence of lymphocytes, we then studied this cytokine in vitro on primary cultured podocytes from immune-deficient mice (Rag2(-/-)Il2rg(-/-) and Rag2(-/-)Il2rb(-/-)) compared to controls. IL-15 induced downstream activation of JAK1/3 and SYK in primary cultured podocytes. IL-15-dependent JAK/SYK induction was impaired in the absence of γC or IL-2Rβ. We found γC largely induced on podocytes during human glomerulonephritis. Thus, renal lesions are indeed modulated by intrinsic glomerular cells through the γC/IL-2Rβ receptor response, to date classically described only in immune cells.
Neidig, Lauren E; Owston, Michael A; Ball, Erin; Dick, Edward J
Crescentic glomeruli are the hallmark finding in rapidly progressive glomerulonephritis (RPGN) and are characterized by disruption and proliferation of the glomerular capsule and an influx of cells into Bowman's space. Pauci-immune-type RPGN is identified by a lack of immunoglobulins and immune complexes in the glomerular basement membrane. Complete necropsy and histology were performed on the affected chimpanzee. Electron microscopy was performed on kidney sections. A search of the literature was performed to identify spontaneous RPGN in animals. We report a case of crescentic glomerulonephritis of the pauci-immune-type in a hepatitis C virus-infected 28-year-old male chimpanzee (Pan troglodytes) who was humanely euthanized for a cardiac-related decline in health. To our knowledge, this is the first report describing pauci-immune crescentic glomerulonephritis in a non-human primate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Ooi, B S; Cohen, D J; Veis, J H
The mesangial cell occupies a central position in the genesis of the pertubations occurring during the pathogenesis of glomerulonephritis. In vitro studies have shown that this cell is a metabolically active cell producing a variety of cytokines which act as autocoids; such cytokines are also liberated by the monocytes/macrophages which infiltrate the glomerulus in nephritis. This review summarizes the evidence for the participation of these cytokines in animal models of nephritis and in human renal disease, focusing on the roles of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, colony-stimulating factor-beta, tumor necrosis factor, interleukin-1, and interleukin-6.
Al-Brahim, Nabeel; Zaki, Ashraf H; El-Merhi, Khaled; Ahmad, Mahmoud S
Kaposi sarcoma is a malignant vascular neoplasm uncommonly seen in immunosuppressed patients. Herein we report an unusual case of tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis treated with prednisolone and cyclosporine. The patient presented after 10 months of starting the treatment with a tonsillar mass. Histological examination was typical of monomorphic spindle cell proliferation with slit-like vascular channels. The tumor cells expressed CD34, D2-40 and positive nuclear stain for HHV-8. Kaposi sarcoma is associated with immunosuppression and rarely occurs in the tonsil. Clinicians should be aware of this rare presentation of Kaposi sarcoma.
Moll-Guillen, Jose-Luis; Espí-Reig, Jordi; Blanes-Julia, Marino; García-Martínez, Ana-María; Pujol-Marco, Conrad; Hernández-Jaras, Julio
Levamisole is illicitly employed as a cocaine adulterant. The consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated syndromes. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole. Likewise, patients with ANCA-associated vasculitis (AAV) and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. Here, we report an unusual case of a patient in which kidney biopsy showed membranous glomerulonephritis with cellular crescents associated with levamisole-contaminated cocaine use. PMID:26605317
Sánchez-Cordón, P J; Salguero, F J; Núnez, A; Gómez-Villamandos, J C; Carrasco, L
This article describes a case of glomerulonephritis and immunocomplex (IgM, IgG and C3c) deposition in the mesangium and basement membranes of a 2-year-old dog with canine viral hepatitis and dirofilariasis. The deposits observed in the mesangium were in the vicinity of cells with viral replication. However, no clear relationship was found between viral replication and the deposition of immunocomplexes in the glomerular capillary basement membranes, which may be the reason why these deposits have only been tentatively related to the concomitant infestation by Dirofilaria immitis.
Moscoso-Solorzano, Grace T.; Madureira-Silva, Marcus V.; Balda, Carlos; Franco, Marcello F.; Mastroianni-Kirsztajn, Gianna
Background There are few reports of glomerulonephritis (GN) with crescents and a rapidly progressive course that lead to a diagnosis of a previously unsuspected B-cell dyscrasia. Case Presentation: We report a case of rapidly progressive GN: the patient showed no evidence of etiology at the time of biopsy and was diagnosed as IgA multiple myeloma (MM) during investigation based on a renal biopsy. He presented diffuse proliferative and exudative GN and marked plasma cell infiltration of the kidney. Conclusion The present case raises the possibility that proliferative GN with crescents may be a rare mode of presentation of MM. PMID:22470380
Yamaguchi-Yamada, Misuzu; Akashi, Naotsugu; Goto, Yasufumi; Anan, Sayuri; Yamamoto, Yoshie; Ogura, Atsuo; Manabe, Noboru
The ICR-derived glomerulonephritis (ICGN) mouse is an appropriate model for anemia associated with chronic renal disorder (CRD). Insufficient renal production of erythropoietin (EPO) induces the anemia associated with CRD. EPO mRNA is expressed in both kidneys and liver of progressing-stage ICGN mice. Hypoxic stimulation induced the EPO mRNA expression in the liver as well as in the kidneys of ICGN mice. The localization of EPO-producing cells in the liver remains controversial. Present study using an amplified in situ hybridization technique identified that nonparenchymal cells were the source of hepatic EPO production in ICGN mice under both normoxia and hypoxia.
Babar, Faizan; Posner, Jeffery N.; Obah, Eugene A.
Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects. PMID:27124161
Babar, Faizan; Posner, Jeffery N; Obah, Eugene A
Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects.
Clarkson, A. R.; MacDonald, Mary K.; Cash, John D.; Robson, James S.
Treatment with indomethacin, aspirin, or prednisone has been shown to reduce urinary fibrin/fibrinogen degradation products (F.D.P.) in approximately two-thirds of patients with proliferative glomerulonephritis. This reduction which is dose-dependent for prednisone but not for indomethacin or aspirin in the range of doses used occurs within two to three days of beginning treatment and is thought to result from decreased intraglomerular fibrin deposition rather than alteration of glomerular permeability to F.D.P. In patients who responded in this manner treatment was associated with reductions in the degree of proteinuria and maintenance or improvement in renal function. PMID:5046478
Chen-Chen, Xia; Yadav, Arun Kumar; Kai, Zhang; Yi-Feng, Peng; Qing-Xi, Yuan; Pei-Ping, Zhu; Li-Jin, Feng; Xu-Dong, Xu; A-Shan, Wu; Guang-Yu, Tang
The aim of this study is to investigate microstructural changes in chronic glomerulonephritis (CGN) rabbit model under diffraction enhanced imaging (DEI) technology of synchrotron radiation (SR). The chronic glomerulonephritis (CGN) models were obtained within two months after 5 New Zealand white rabbits were treated with doxorubicin hydrochloride. Blood exams, urine tests and kidney histological studies were carried out after the 5 rabbits were humanely sacrificed by hyperanesthesia. The kidney tissues were fixed in 4% formalin for one week before DEI experiment, with another 5 normal rabbits used as the control group. The experiment was performed at Beijing Synchrotron Radiation Facility (BSRF) with a 4W1A beam line (beam energy was 14keV). On routine scanning process, the rocking curve was detected, and slope position on the curve was selected to make a 360° spatial CT scan; DEI reconstruction software was used to generate a 3-dimensional image, from which the difference in grey value between the chronic glomerulonephritis (CGN) group and the control group was measured and analyzed using MATLAB and SPSS. Without radio-contrast, DEI provided clear visibility of the microstructures including artery, vein, straight collecting ducts, papillary tubules, glomeruli in both the chronic glomerulonephritis (CGN) group and the control group, with a spatial resolution as low as 10μm. MATLAB grey value extraction and SPSS analysis showed that cortex of CGN group (91 to 112) lost more gray value compared to the control group (121 to 141), T tests P < 0.05. Equivalant cortical ROI (data points 450×80) quantitative analysis showed that gross grey value of CGN group (ranking from 55 to 160) was smaller than the control group (ranking from 75 to 175). DEI images correlated well with pathologic images. Morphological changes in the microstructure of contstartabstractCGN kidney was revealed, due to the advantage of phase-contrast imaging (PCI) mechanism, and the diagnostic
Rampelli, S K; Rajesh, N G; Srinivas, B H; Harichandra Kumar, K T; Swaminathan, R P; Priyamvada, P S
There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04-0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022).
Park, Chuiyoung; Choi, Seung Won; Kim, Misung; Park, Jongha; Lee, Jong Soo; Chung, Hyun Chul
Hypocomplementemic urticarial vasculitis syndrome is a rare disorder characterized by chronic urticarial vasculitis, arthralgia, arthritis, and hypocomplementemia. Previously, only six patients with concomitant hypocomplementemic urticarial vasculitis syndrome, Jaccoud's arthropathy, and valvular heart disease have been reported. A 30-year-old Korean man presented with hypocomplementemic urticarial vasculitis syndrome. In addition to urticarial cutaneous lesions, he experienced polyarthralgia and arthritis that resulted in progressive deformity of the joints of both hands, cardiac valvulopathy with mitral, tricuspid, and aortic regurgitation, and intermittent neck swelling with laryngeal edema. He also developed nephritis with azotemia. His renal biopsy results revealed membranoproliferative glomerulonephritis, type I. He showed a partial response to a combination therapy of steroid, cyclophosphamide, and mycophenolate mofetil. We describe, to the best of our knowledge, the first case of glomerulonephritis presenting a arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis syndrome. A combination of corticosteroids, cyclophosphamide, and mycophenolate mofetil appear to be a safe and effective treatment for nephropathy, however are less effective for cutaneous vasculitis, cardiac valvulopathy, and arthropathy.
Introduction Hypocomplementemic urticarial vasculitis syndrome is a rare disorder characterized by chronic urticarial vasculitis, arthralgia, arthritis, and hypocomplementemia. Previously, only six patients with concomitant hypocomplementemic urticarial vasculitis syndrome, Jaccoud’s arthropathy, and valvular heart disease have been reported. Case presentation A 30-year-old Korean man presented with hypocomplementemic urticarial vasculitis syndrome. In addition to urticarial cutaneous lesions, he experienced polyarthralgia and arthritis that resulted in progressive deformity of the joints of both hands, cardiac valvulopathy with mitral, tricuspid, and aortic regurgitation, and intermittent neck swelling with laryngeal edema. He also developed nephritis with azotemia. His renal biopsy results revealed membranoproliferative glomerulonephritis, type I. He showed a partial response to a combination therapy of steroid, cyclophosphamide, and mycophenolate mofetil. Conclusions We describe, to the best of our knowledge, the first case of glomerulonephritis presenting a arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis syndrome. A combination of corticosteroids, cyclophosphamide, and mycophenolate mofetil appear to be a safe and effective treatment for nephropathy, however are less effective for cutaneous vasculitis, cardiac valvulopathy, and arthropathy. PMID:25339233
Motiram Kakalij, Rahul; Tejaswini, G; Patil, Madhoosudan A; Dinesh Kumar, B; Diwan, Prakash V
Preclinical Research Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally-induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune-complex glomerulonephritis in female BALB/c mice. Pre-immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF-α levels. Co-administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171-179, 2016. © 2016 Wiley Periodicals, Inc.
Maratou, Klio; Behmoaras, Jacques; Fewings, Chris; Srivastava, Prashant; D’Souza, Zelpha; Smith, Jennifer; Game, Laurence; Cook, Terence; Aitman, Tim
Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity. PMID:21179115
Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud
T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis.
Nagai, Kei; Usui, Joichi; Noguchi, Kazuyuki; Unai, Kei; Hiwatashi, Akira; Arakawa, Yoh; Togashi, Amane; Morito, Naoki; Saito, Chie; Yoh, Keigyou; Tsuruoka, Syuichi; Kojima, Hiroshi; Aita, Kumi; Nagata, Michio; Yamagata, Kunihiro
Renal involvement is a significant complication of multicentric Castleman's disease (MCD) and various glomerular involvements have been reported. A 45-year-old Japanese man presented with persistent proteinuria, with lymphadenopathy and hypergammaglobulinemia. He had been diagnosed 4 years previously with MCD. As his renal impairment had progressed to renal failure, he underwent a renal biopsy. Histology revealed diffuse and global membranous lesions with large and heterogeneous epimembranous deposits. In addition, mesangial cell proliferation and focal extracapillary lesions were found. Under immunofluorescence, granular staining for anti-IgG, IgG1, IgG2 and IgA was strongly positive in the capillary loop, and weakly positive in the mesangium. As such, there was a diversity of histological features. Our perspective with regard to pathogenesis is that the formation of the immune-complex contributed to the membranoproliferative glomerulonephritis type 3-like lesion. This histological multiform with MCD is valuable for increasing our understanding of the mechanism for onset of immune-complex glomerular deposition and cellular proliferation of glomerulonephritis.
Background Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder that is characterized by the development of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/day, and ADPKD is rarely associated with nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN). To date, myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CrGN) has not been reported in a patient with ADPKD. Case presentations We report two cases of MPO-ANCA positive ADPKD. A 60-year-old Japanese woman (case 1) and a 54-year-old Japanese woman (case 2) presented with RPGN featuring severe proteinuria and microscopic hematuria. In both patients percutaneous needle biopsy of the kidney revealed MPO-ANCA-associated CrGN with a paucity of glomerular immunoglobulin staining. Each patient received intravenous methylprednisolone for 3 days, followed by oral prednisolone. Case 1 showed gradual improvement and has not progressed to end-stage renal disease (ESRD), but case 2 developed ESRD requiring hemodialysis within one month despite treatment. Conclusion These are the first two reported cases of MPO-ANCA-associated CrGN in patients with ADPKD. Our experience suggests that serial measurement of the ANCA titer and renal biopsy should be considered for accurate diagnosis and appropriate treatment of ADPKD patients who present with proteinuria, hematuria, and rapid decline of renal function. PMID:23617397
Sandhu, Gagangeet; Casares, Pablo; Farias, Antony; Ranade, Aditi; Jones, James
Pulmonary renal syndrome (PRS) is a combination of diffuse pulmonary haemorrhage and glomerulonephritis (GN). Though an established form of presentation in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated GN and vasculitis, diffuse pulmonary haemorrhage is extremely unusual in those with ANCA-negative GN. We present here a case of a 76-year-old Hispanic female with stage IV chronic kidney disease (serum creatinine of 2 mg/dL), who presented with diffuse alveolar haemorrhage and nephritic syndrome. Less than 1 week prior to the full-blown PRS, she was treated for an apparent pneumonia as was evidenced by a right lower lobe infiltrate on her chest X-ray. Retrospectively, this was likely a focal pulmonary haemorrhage. ANCA were persistently negative, and the remainder of her immunologic workup was normal. Renal biopsy was diagnostic of crescentic pauci-immune GN. The patient required a ventilator and haemodialysis support (serum creatinine 6 mg/dL), and was successfully treated with methylprednisolone, cyclophosphamide and a total of six cycles of plasmapheresis. Once her oliguria resolved, the creatinine plateaued at 2.7 mg/dL. Our case illustrates that diffuse alveolar haemorrhage can be a distinct clinical feature even in patients with ANCA-negative pauci-immune crescentic glomerulonephritis.
Maratou, K; Behmoaras, J; Fewings, C; Srivastava, P; D'Souza, Z; Smith, J; Game, L; Cook, T; Aitman, T
Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. Wistar-Kyoto (WKY) rats show marked susceptibility to CRGN, whereas Lewis rats are resistant. Glomerular injury and crescent formation are macrophage dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterized Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% false discovery rate) for basal and LPS-stimulated macrophages. Moreover, we identified eight genes with differentially expressed alternatively spliced isoforms, by using an in-depth analysis at the probe level that allowed us to discard false positives owing to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7 and define groups of genes that play a significant role in differential regulation of macrophage activity.
Villaro, J; Sánchez Ibarrola, A; Purroy, A
To study the participation of the Hageman factor-related contact system of plasma in the pathogenesis of glomerulonephritis (GN), an anti-BM GN was induced in a group of 10 normal Brown Norway rats and another of seven Brown Norway BN/Mai Pfd f rats. The latter strain is characterized by a congenital deficiency of plasma prekallikrein and of high-molecular weight kininogen, with lengthening of the activated partial thromboplastin time. In the deficient group, one animal developed crescents in less than 25% of glomeruli, five in 25-50% and one in 50-75%. In the group of normal rats, extracapillary proliferation was of greater severity: one animal showed crescents in less than 25% of glomeruli, two in 50-75% and five in more than 75% of glomeruli. Although in both groups intense glomerular fibrin deposition was documented, the intensity of these deposits was less severe in the deficient animals. These data suggest, in the first place, that functional integrity of the contact system is not a necessary requirement for glomerular fibrinogenesis, other mechanisms being implicated in this phenomenon. On the other hand, this functional deficit has exerted a protective effect on crescent formation, which suggests that the contact system can play a role as a mediator of injury in glomerulonephritis, perhaps through the release of contact system-dependent mediators of inflammation. PMID:3396222
Alexander, Mariam P; Fervenza, Fernando C; De Vriese, An S; Smith, Richard J H; Nasr, Samih H; Cornell, Lynn D; Herrera Hernandez, Loren P; Zhang, Yuzhou; Sethi, Sanjeev
C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent.
Lumsden, J S; Russell, S; Huber, P; Wybourne, B A; Ostland, V E; Minamikawa, M; Ferguson, H W
Chinook salmon from New Zealand were shown to have a generalized membranous glomerulonephritis that was most severe in large fish. Marked thickening of the glomerular basement membrane was the most consistent lesion, with the presence of an electron-dense deposit beneath the capillary endothelium.Severely affected glomeruli also had expansion of the mesangium and loss of capillaries,synechiae of the visceral and parietal epithelium and mild fibrosis of Bowmans capsule. Chinook salmon from British Columbia, Canada with bacterial kidney disease caused by Renibacterium salmoninarum had similar histological lesions. They also had thickened glomerular basement membranes that were recognized by rabbit antiserum to rainbow trout immunoglobulin. This was true only when frozen sections of kidney were used and not formalin-fixed tissue. An attempt to experimentally produce a glomerulopathy in rainbow trout by repeated immunization with killed R. salmoninarum was not successful. Case records from the Fish Pathology Laboratory at the University of Guelph over a 10-year period revealed that a range of species were diagnosed with glomerulopathies similar to those seen in Chinook salmon. The majority of these cases were determined to have chronic inflammatory disease. This report has identified the presence of immunoglobulin within thickened basement membranes of Chinook salmon with glomerulonephritis and supports the existence of type III hypersensitivity in fish.
Kamenetskiĭ, M S; Pervak, M B; Tkachenko, G D; Vernikov, B L
To develop criteria for determining predisposition to pulmonary edema in patients with glomerulonephritis, clinical, laboratory and X-ray examinations were made in 697 patients with glomerulonephritis at different stages of its development. X-ray examination included chest tele X-ray and its densitometric analysis. Twenty two patients underwent computerized tomography with histographic analysis. In 106 patients, X-ray findings were compared with the volume of circulating blood, cardiac and stroke indices. Changes in the lungs and pleural cavities were found in 22.7%, pulmonary edema was revealed in 15.7% of the patients. The prognostically unfavourable criteria for the development of pulmonary edema were found to be Stage II pulmonary venous hypertension with hypervolemia and peripheral edemas. The densitometrically detected increase in the density of the lower lungs in patients with Stage II venous hypertension suggests early manifestations of interstitial edema of the lung and the narrowing of the histogram angle limited by its ascending and descending lines is indicative of the fact that interstitial edema progresses to alveolar one.
Fernández, J; Colomé, Jaime Fernández; Sanz-Gallén, P; Sanz-Gallén, Pere; Nogué, S; Xarau, Santiago Nogué
For several years we carried out a follow-up of two patients with IgA mesangial glomerulonephritis with antecedents of exposure to toxic substances (cadmium and organic solvents). The first case involved a 47 year old male who was diagnosed with mesangial IgA glomerulonephritis eight years ago; he had been working for twelve years as a solderer. He had used metal bars containing 25% cadmium as part of the soldering material. Very high levels of cadmium were detected in his blood and urine. The second case involved a 50 year male who was exposed to a wide number of organic dissolvents for 23 years. Three years ago he was diagnosed with a proliferative diffuse mesangial glomerulonephritis with IgA deposits; in spite of that, the patient continued working until one year ago, when was found to have a chronic stage 3 renal disease secondary to IgA nephropathy. Patients diagnosed with mesangial IgA glomerulonephritis should be kept apart from exposure to nephrotoxic substances.
Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio
Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes.
Martínez-Odriozola, P; Gutiérrez-Macías, A; Moina Eguren, I; Arrieta Lezama, J
We report a case of idiopathic retroperitoneal fibrosis and rapidly progressive glomerulonephritis with serum antiproteinase 3 antineutrophil cytoplasmic antibodies (anti-PR3-ANCA), without clinical or histological signs of Wegener's granulomatosis, in a 46-year-old man. Our case and previously reported cases showing the same association support the hypothesis that the association is not fortuitous, but reflects a common immunological mechanism.
Sutmuller, M; Baelde, H J; Tysma, O M; de Heer, E; Bruijn, J A
Chronic graft-versus-host disease (GvHD) in mice is a model resembling glomerulonephritis in human systemic lupus erythematosus. In the present study congenic mouse strains were used to investigate the pathogenetic role of (1) donor T cell subset chimerism and (2) donor thymocytes in this model. In GvHD employing minor lymphocyte-stimulating-1 (Mls-1)-compatible donors and recipients, full-blown immune complex glomerulonephritis was associated with a low-donor CD8(+) T cell chimerism. Injection of lymphocytes from Mls-1-negative donors (Mls-1(b)) into Mls-1-positive recipients (Mls-1(a)) induces a type of GvHD characterized by rapid self-limitation accompanied by the immediate inhibition of donor T cell chimerism and the absence of glomerulonephritis. However, omission of thymocytes from the donor inoculate does result in glomerular depositions containing immunoglobulins. These results suggest that donor CD8(+) T cell chimerism is associated with attenuation of immune complex glomerulonephritis, whereas Mls-1-incompatible donor T cell precursors prevent the disease. Copyright 1998 Academic Press.
... glomeruli. The glomeruli of the kidney help filter wastes and fluids from the blood to form urine. ... the glomerular basement membrane. This membrane helps filter wastes and extra fluids from the blood. Damage to ...
Hsieh, Yao-Peng; Wen, Yao-Ko
A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.
Farooqui, M; Alsaad, K; Aloudah, N; Alhamdan, H
We report a case of idiopathic membranoproliferative glomerulonephritis (MPGN) recurring 2 years after a living-unrelated kidney transplantation. The disease was refractory to intravenous immunoglobulin and plasmapheresis. Treatment with 2 doses of rituximab resulted in remission of the disease. The disease relapsed 18 months later after an episode of cytomegalovirus pneumonitis. After treatment of the pneumonitis, a lung biopsy was performed owing to persistent chest symptoms, which revealed bronchiolitis obliterans with organizing pneumonia. Bone marrow examination and culture revealed presence of acid-fast bacilli, and culture grew Mycobacterium tuberculosis. A repeated course of rituximab was withheld because of infection with tuberculosis, the patient's chest symptoms, and rare reports of noninfectious lung disease after the use of rituximab. The patient continues to have proteinuria with impaired kidney function. Copyright © 2015 Elsevier Inc. All rights reserved.
Sathyanarayanan, Vishwanath; Razak, Abdul; Narayan, Girish; Prabhu, Mukhyaprana; Ramachandran, Balasubramanian; Ranjini, Kudva; Vidya, Monappa; Joshi, Kusum
Posterior reversible encephalopathy syndrome (PRES) is a rare complication of nephrotic syndrome and corticosteroid therapy. Here, we discuss an 18 year old man with type 1 membranoproliferative glomerulonephritis (MPGN) secondary to hepatitis B infection who developed posterior leukoencephalopathy while on therapy with lamivudine and prednisone. He developed seizures and vision loss. He also had hypertension, but no sudden elevation was recorded at any time. Magnetic resonance imaging revealed patchy areas of altered signal intensity involving cortical gray and subcortical white matter in the bilateral frontoparietal regions, occipital cortices, temporal cortices and cerebellar hemispheres, and hyperintensity on T2W and FLAIR sequences. Tapering of prednisone and controlling hypertension resulted in clinical improvement within a few days, and in a month MRI was normal. Diagnosing PRES requires a high index of suspicion when treating similarly susceptible patients. PRES as a complication during the treatment of MPGN secondary to hepatitis B has, to our knowledge, never been reported previously in the literature.
Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P
In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.
Campbell, G Adam; Hu, Daniel; Okusa, Mark D
Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.
Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir; Thorlund, Kristian; Bruchfeld, Annette; Guillevin, Loic; Haubitz, Marion; Merkel, Peter A.; Peh, Chen Au; Pusey, Charles; Jayne, David
Background Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized control trials of plasma exchange for renal vasculitis. Study Design Systematic review and meta-analysis of manuscripts identified from electronic databases, bibliographies, and studies identified by experts. Data was abstracted in parallel by two reviewers. Setting & Population Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange Outcome Composite of end-stage renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model the pooled relative risk of end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared to standard care alone (95% confidence interval 0.65 to 0.99; p=0.04). No significant heterogeneity was detected (p=0.5; I2=0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (p=0.7) or number of plasma exchange treatments (p=0.8). The relative risk for end-stage renal disease was 0.64 (95% confidence interval 0.47 to 0.88; p=0.006) while the relative risk for death alone was 1.01 (95% confidence interval 0.71 to 1.4; p=0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliable determine if plasma exchange reduces the composite of end-stage renal disease or death. Conclusions Plasma exchange may reduce the composite endpoint of end-stage renal disease or death in renal vasculitis. Further trials are required given the limited data available. PMID:21194817
Sánchez-Agesta Martínez, Marina; Rabasco Ruiz, Cristina; Sánchez Sánchez, Rafael; Ortega Salas, Rosa; López Andreu, María; Aljama García, Pedro; Espinosa Hernández, Mario
Type iii extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN. The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. All patients diagnosed of PEGN from 1995 to 2015 (n=72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. Positive staining for C3 was observed in 22 out of the 72 patients (30.5%). At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85mg/dl, P=0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (P=0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
Gupta, A.; Agrawal, V.; Kaul, A.; Verma, R.; Pandey, R.
Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disease that most commonly presents as rapidly progressive glomerulonephritis with or without pulmonary involvement. It is characterized by the presence of antibodies directed to antigenic targets within glomerular and alveolar basement membranes. This study was performed to evaluate the clinicopathological features and outcome in anti-GBM crescentic glomerulonephritis (CrGN) at a tertiary care center in North India over a period of 9 years (January 2004 to December 2012). A diagnosis of anti-GBM CrGN was made in the presence of >50% crescents, linear deposits of IgG along GBM, and raised serum anti-GBM antibody titer. Of 215 cases of CrGN diagnosed during this period, 11 had anti-GBM CrGN. Anti-GBM CrGN was found at all ages but was most common in the third to fifth decade with no gender predilection (mean age 48 +/- 15 years, 13–67 years). Patients presented with a mean serum creatinine of 10.2 +/- 5.3 mg/dl and sub-nephrotic proteinuria. Pulmonary involvement was present in two patients. Myeloperoxidase-antineutrophil cytoplasmic antibody was positive in two (2/11) elderly patients. Follow-up was available in four patients for a range of 30-270 (mean 99.5 ± 114.5) days, two remained dialysis dependent while two died due to uremia and sepsis. Our findings show that anti-GBM disease is a rare cause of CrGN in India, accounting for only 5% of patients. It usually presents as a renal-limited disease and is associated with a poor renal outcome. PMID:27795626
Salvadori, Maurizio; Rosso, Giuseppina
This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560
Hohenstein, Bernd; Daniel, Christoph; Johnson, Richard J; Amann, Kerstin U; Hugo, Christian P M
Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibα antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse.
Shen, Peicheng; Yang, Xuejun; He, Liqun
To investigate the effect of the traditional Chinese herbs Astragali and Angelicae Sinensis (A & As) particle [contains Huangqi (Radix Astragali Mongolica), Danggui (Radix Angelicae Sinensis), Huzhanggeng (Rhizoma Polygoni Cuspidati) and Danshen (Radix Salviae Miltiorrhizae)] on proteinuria in glomerulonephritis patients with stage 2 chronic kidney disease. A prospective, multi-center, and randomized controlled clinical trial was performed for 24 weeks. From March 2011 to April 2012, 158 patients from nine hospitals in China participated. They were randomized into the A & As group (79 cases, A & As particle 15.2 g/day) and losartan group (79 cases, losartan 50 mg/day). At each follow-up visit, clinical data including blood pressure, urinalysis, 24-h-urinary protein excretion, serum albumin and serum creatinine were collected. All 158 patients completed the follow-up. Proteinuria in the losartan group exhibited a biphasic time-dependent decline with a significant steady reduction from baseline to week 12 (P = 0.0014), and a platform level during the remaining 12-week follow-up (P > 0.05). In contrast, there was a continual significant decrease of proteinuria in the A & As group (P < 0.001). When compared with the losartan results, proteinuria in the A & As group from week 16 to week 24 was significantly reduced (P < 0.001). Stable eGFRs and blood pressure were also observed in both groups. Medication side effects were minimal and non-fatal. For Chinese glomerulonephritis patients with stage 2 chronic kidney disease, therapy with A & As particles may provide effective anti-proteinuria treatment.
Abraham, Abu P; Ma, Frank Y; Mulley, William R; Nikolic-Paterson, David J; Tesch, Greg H
MMP-12 (macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP-12 is highly up-regulated in experimental anti-glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP-12 is required for glomerular macrophage infiltration and crescent formation in anti-GBM glomerulonephritis. Accelerated anti-GBM disease was induced in groups of MMP-12 gene deficient mice (MMP-12-/-) and wild type C57BL/6 J (WT) controls, which were killed 12 days after injection of anti-GBM serum. WT and MMP-12-/- mice developed glomerular damage and glomerular tuft adhesions to Bowman's capsule. Both groups developed severe proteinuria. WT mice also developed significant loss of renal function and crescents in 22% of glomeruli, which were associated with macrophage infiltration and Bowman's capsule rupture. In contrast, MMP-12-/- mice were partially protected from renal function decline, crescent formation and Bowman's capsule rupture. This was associated with reduced macrophage infiltration in both glomeruli and the interstitium, and with reduced expression of CCL2, TNF-α and iNOS mRNA in MMP12-/- kidneys. In addition, KIM-1 mRNA levels were reduced in MMP-12-/- mice indicating less tubular damage. These data demonstrate that endogenous MMP-12 facilitates macrophage accumulation and activation in anti-GBM glomerulonephritis which is required for glomerular crescent formation, Bowman's capsule rupture, tubular damage and renal function decline. This article is protected by copyright. All rights reserved.
L'Imperio, Vincenzo; Smith, Andrew; Chinello, Clizia; Pagni, Fabio; Magni, Fulvio
Glomerulonephritis (GN) is one of the most common origins of chronic kidney disease and its careful evaluation is crucial for prognostic and therapeutic purposes, with the renal biopsy still playing a central role for the diagnosis. However, due to its invasiveness, it is not devoid of complications and many investigations have focused on identifying biomarkers for chronic kidney diseases using less-invasive and easy-to-collect samples, such as urine and blood. In this context, proteomics has played a crucial role in determining the molecular changes related to disease progression and early pathological glomerular modifications. Here, we report a review of selected literature for each GN, based on selected works published in the last 10 years, showing how these approaches have generated clinically relevant findings in the study of glomerulonephritis. We also describe several proteomic strategies, highlighting their technical advantages and limitations, future perspectives for proteomic applications in the study of GNs, and their possible application in routine practice.
Reynolds, John; Preston, Gloria A.; Pressler, Barrak M.; Hewins, Peter; Brown, Michael; Roth, Aleeza; Alderman, Elizabeth; Bunch, Donna; Jennette, J. Charles; Cook, H. Terence; Falk, Ronald J.; Pusey, Charles D.
‘Autoantigen complementarity’ is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is ‘antisense/complementary’ to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that ‘complement’ the well characterized epitope on α3(IV)NC1, pCol(24–38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24–38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24–38) sequence. Interestingly, anticomplementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for ‘autoantigen complementarity’ in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected ‘complementary’ antigens. PMID:25841937
Fujita, Emiko; Shimizu, Akira; Masuda, Yukinari; Kuwahara, Naomi; Arai, Takashi; Nagasaka, Shinya; Aki, Kaoru; Mii, Akiko; Natori, Yasuhiro; Iino, Yasuhiko; Katayama, Yasuo; Fukuda, Yuh
Macrophages are heterogeneous and include classically activated M1 and alternatively activated M2 macrophages, characterized by pro- and anti-inflammatory functions, respectively. Macrophages that express heme oxygenase-1 also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects of statin in experimental anti-glomerular basement membrane glomerulonephritis and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti-glomerular basement membrane glomerulonephritis and treated with atorvastatin (20 mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7, together with increased mRNA levels of the M1 macrophage-associated cytokines, interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. In contrast, statin reduced the level of proteinuria, reduced infiltration of macrophages in glomeruli with suppression of monocyte chemotactic protein-1 expression, and inhibited the formation of necrotizing and crescentic lesions. The number of glomerular ED3-positive macrophages decreased with down-regulation of M1 macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2 macrophages with up-regulation of the M2 macrophage-associated chemokines and cytokines, chemokine (C-C motif) Iigand-17 and interleukin-10. Statin also increased the glomerular interleukin-10-expressing heme oxygenase-1-positive macrophages. Statin inhibited macrophage development, and suppressed ED3-positive macrophages, but augmented ED2-positive macrophages in M2-associated cytokine environment in vitro. We conclude that the anti-inflammatory effects of statin in glomerulonephritis are mediated through inhibition of macrophage infiltration as well as augmentation of anti-inflammatory macrophages.
The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral
Kitching, A Richard; Turner, Amanda L; Semple, Timothy; Li, Ming; Edgtton, Kristy L; Wilson, Gabrielle R; Timoshanko, Jennifer R; Hudson, Billy G; Holdsworth, Stephen R
IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV)NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response
Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.
IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829
Heeringa, Peter; van Goor, Harry; Itoh-Lindstrom, Yoshie; Maeda, Nobuyo; Falk, Ronald J.; Assmann, Karel J. M.; Kallenberg, Cees G. M.; Jennette, J. Charles
Nitric oxide (NO) radicals generated by endothelial nitric oxide synthase (eNOS) are involved in the regulation of vascular tone. In addition, NO radicals derived from eNOS inhibit platelet aggregation and leukocyte adhesion to the endothelium and, thus, may have anti-inflammatory effects. To study the role of eNOS in renal inflammation, the development of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was examined in mice lacking a functional gene for eNOS and compared with wild-type (WT) C57BL/B6j mice. WT C57BL/6j mice (n = 12) and eNOS knockout (−/−) mice (n = 12) were immunized intraperitoneally with sheep IgG (0.2 mg in complete Freund’s adjuvant). At day 6.5 after immunization, mice received a single i.v. injection of sheep anti-mouse GBM (1 mg in 200 μl PBS). Mice were sacrificed at day 1 and 10 after induction of the disease. All WT mice survived until day 10, whereas 1 eNOS−/− mouse died and 2 more became moribund, requiring sacrifice. At day 10, eNOS−/− mice had higher levels of blood urea nitrogen than WT mice (P < 0.02), although proteinuria was comparable. Immunofluorescence microscopy documented similar IgG deposition in both WT and eNOS−/− mice, but eNOS−/− mice had more extensive glomerular staining for fibrin at day 10 (P < 0.007). At day 10, light microscopy demonstrated that eNOS−/− mice had more severe glomerular thrombosis (P < 0.003) and influx of neutrophils (P < 0.006), but similar degrees of overall glomerular endocapillary hypercellularity and crescent formation. In conclusion, accelerated anti-GBM glomerulonephritis is severely aggravated in eNOS−/− mice, especially with respect to glomerular capillary thrombosis and neutrophil infiltration. These results indicate that NO radicals generated by eNOS play a protective role during renal inflammation. PMID:10702405
Dewan, Deepak; Gulati, Sanjeev; Sharma, Raj K; Prasad, Narayan; Jain, Manoj; Gupta, Amit; Kumar, Alok
Crescentic glomerulonephritis (CsGN) is an uncommon entity in children. This prospective study was conducted to evaluate the aetiology, clinical spectrum and outcome in children with crescentic glomerulonephritis. The single-centre prospective study comprised of 22 children with biopsy proven CsGN who had been referred to our institute over the period January 2000 to December 2005. These patients were subjected to detailed clinical and biochemical examinations. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide with or without plasmapheresis. All patients received supportive care, including control of hypertension and oedema and supportive management of renal insufficiency. During this 5-year period, CsGN accounted for 5.1% of all biopsies done in children. The mean age was 12.27 years (range 4 years to 18 years). There were eight girls and 14 boys. The mean duration of symptoms prior to referral was 2.47 months (range 5 days to 21 months). Aetiology was immune complex in 19 cases, anti-glomerular basement membrane (anti-GBM) antibody disease in two cases and pauci-immune (Wegener's granulomatosis) in one case. The percentage of crescents ranged from 50% to 100% (mean 70.6%). Twenty-one out of 22 (95.5%) children in our series had hypertension at presentation that required treatment with antihypertensive medications. The serum creatinine level at presentation ranged from 1.5 mg/dl to 11.4 mg/dl (mean 5.5 mg/dl). Of the 22 children, two were lost to follow-up, while the mean follow-up period of the rest of the 20 children was 8.13 months (range 1 month to 43 months). At the last follow-up of the 22 children, ten had stage 5 chronic kidney disease (CKD) and three had stage 4 CKD, while seven children had a calculated glomerular filtration rate (GFR) of >60 ml/min per 1.73 m(2) body
Barnes, J. L.; Torres, E. S.; Mitchell, R. J.; Peters, J. H.
Fibronectin (Fn) plays an important role in tissue remodeling during embryogenesis, wound repair, and vascular disease, and is thought to regulate cellular processes such as cell adhesion, migration, proliferation, and differentiation through specialized domains within the molecule. In addition, Fn can be alternatively spliced at three regions: extradomains EIIIA, EIIIB, and a variable segment V, potentially giving rise to functionally distinct variants of the molecule. We have previously shown a sequential expression of cellular Fn first by platelets, followed by macrophages, then mesangial cells in habu snake venom-induced proliferative glomerulonephritis (Am J Pathol 145: 585-597, 1994). These studies examined the cellular sources and glomerular localization of Fn in general but did not distinguish between the various alternatively spliced isoforms. In this study, we examine by in situ hybridization and immunohistochemistry the temporal expression and cellular sources of EIIIA, EIIIB, and V in a model of proliferation glomerulonephritis that has cell migration, proliferation, and extracellular matrix synthesis as features of tissue remodeling. Macrophages were the first cells to express Fn mRNA showing an EIIIA+, EIIIB-, and V95+ pattern beginning at 8 hours after habu snake venom injection. Migrating mesangial cells at the margins of early lesions (8 and 24 hours) did not overexpress mRNA encoding these Fn variants, but immunofluorescence microscopy revealed V95 and EIIIA protein at the margins of lesions. EIIIB was absent in lesions at this time. At 48 hours and peaking at 72 hours after habu snake venom injection, mesangial cells in central aspects of glomerular lesions expressed abundant mRNA and protein for V95 and EIIIA. EIIIB mRNA and protein was slight in the mesangium at these times. Parietal epithelial cells, particularly adjacent to glomerular lesions, also expressed abundant mRNA and protein for all three variants throughout the course of the disease
Sugiura, Tokio; Yamada, Takuji; Kimpara, Yuri; Fujita, Naoya; Goto, Kenji; Koyama, Norihisa
Hepatitis C virus (HCV) infection leads to chronic liver disease, but it has also been associated with extrahepatic manifestations. Membranoproliferative glomerulonephritis (MPGN) is the most common renal disease associated with HCV. Although renal disease related to HCV in adults has been well studied, it has not been well studied in children because it is rare. A recent study found that antiviral therapy was effective for adult patients with HCV-associated MPGN. We report a 9-year-old girl with HCV-associated MPGN. Her HCV genotype was 1b, and her virus load was high. The first renal biopsy showed mesangial proliferation and partial double contours of the basement membrane on light microscopy and immunofluorescence staining with immunoglobulin (Ig) M, IgG, and C3. The patient was successfully treated with pegylated interferon (IFN) alpha-2a monotherapy. The antiviral therapy was generally well tolerated. After antiviral therapy, a sustained virological response-defined as negative HCV ribonucleic acid (RNA) at least 24 weeks after antiviral treatment-was achieved, the proteinuria disappeared, and the second renal biopsy showed improvement.
Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou
Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction–chromatography– mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool. PMID:26443483
Mori, Yutaro; Ihara, Katsuhito; Yamaguchi, Wakaba; Fujii, Tetsuro; Toda, Takayuki; Nagata, Michio; Matsui, Noriaki
A 26-year-old man diagnosed with nephrotic syndrome was administered steroid monotherapy. Urinary protein excretion was 2-3 g/day despite the therapy. Percutaneous renal biopsy revealed Type I idiopathic membranoproliferative glomerulonephritis (IMPGN). Although intravenous steroid therapy at the dose of 1,000 mg/day for 3 days was administered, proteinuria persisted at the level of 1 g/day. Renal dysfunction (cystatin C, 1.33 mg/L) was evident. Strong inflammation was suggested by occult blood (3+) and urinary (red blood cells: 30-50/high power field) sediment. We considered steroid monotherapy to be ineffective, and initiated combina-tion therapy with mycophenolate mofetil (MMF) and steroids. Consequently, urinary protein excretion moderately decreased to 0.34 g/day without adverse events or worsening of the renal function. The steroid quantity could be reduced without relapse. Subsequently, we were able to reduce the dose of MMF gradually, then terminated the medication. IMPGN is a rare disease with a poor renal prognosis. Recently, MMF therapies for IMPGN have been attempted, but there are few cases in Japan. Our case suggests that combination therapy with MMF and steroids is effective and safe for treating IMPGN.
Tovbin, David; Shnaider, Alla; Kachko, Leonid; Basok, Anna; Vorobiov, Marina; Rogachev, Boris; Abramov, Dan; Zlotnik, Moshe
Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in IgA nephropathy (IgAN) in renal transplant patients on immunosuppressive therapy. RPGN post ischemia-reperfusion has not been previously reported. We report a 62 year old male patient on azathioprine therapy, 9 years after left cadaveric renal transplantation due to end stage renal disease of unknown etiology, who presented with progressive deterioration in renal function and hematuria. Renal biopsy was consistent with IgAN. Duplex and CT scan demonstrated a decreased renal graft perfusion, due to severe atherosclerosis and stenosis of iliac arteries. The patient underwent left axilo-femoral bypass graft surgery with improvement in kidney graft perfusion and function. However, few weeks later, patient presented with pulmonary edema and advanced renal failure and he was initiated on hemodialysis. Repeated renal biopsy demonstrated crescentic GN. To the best of our knowledge, this is the first report of RPGN following reversal of ischemia and reperfusion. There was no evidence for atherembolic disease which is not uncommon after vascular surgery and it has been reported to be rarely associated to crescentic GN. Theoretical explanations for exacerbation of IgAN to crescentic GN, following successful reperfusion, could be enhancement of capillary damage, inflammation and oxidative stress. Putative mechanisms for these phenomena may be interaction of reperfusion-induced hyperfiltration, high intraglomerular capillary pressure, oxidative stress, increased polymorphonucler cells infiltration and inflammation; the presence of IgA immune deposits and azathioprine metabolites, both can also be associated to enhancement of oxidative stress.
Andreenko, G V; Poliantseva, L R; Podorol'skaia, L V; Bumblite, I D
To estimate the individual role of the plasminogen activators (PA) urokinase (u-PA) and tissue (t-PA) in the development of two renal diseases (the nephrotic forms of chronic glomerulonephritis (CGN) and amyloidosis, the baseline plasma and urine levels of u-PA and t-PA antigens, their functional activity (FPAA), and changes in these parameters were determined after protein loading test (0.7 g/kg). In healthy individuals and patients with amyloidosis, the baseline FPAA changes from 0 to the maximum were caused only by the alterations of u-PA levels, in those with CGN, they were induced by the changes in the content of u-PA and t-AP antigens. The functional loading test revealed PA reserves solely in patients having a high baseline FPAA for both nephropathies: u-PA in amyloidosis and t-PA in CGN. In all the patients, the urine levels of u-PA antigens were 20-40 times more than those of t-PA antigens and 5-6 times less than those plasma u-PA. The findings suggest that urokinase may be regarded as the major plasminogen activator involved in CGN and amyloidosis.
Al-Ghaithi, Badria; Chanchlani, Rahul; Riedl, Magdalena; Thorner, Paul; Licht, Christoph
Post-infectious glomerulonephritis (PIGN) usually follows a benign course, but few children have an atypical, severe presentation, and these exceptional cases have been linked to the dysregulation of the complement alternative pathway (CAP). There is a considerable overlap in the histopathological features of PIGN and C3 glomerulopathy (C3G), which is also associated with CAP dysregulation but has a poorer outcome. We hypothesized that PIGN and C3G define a disease spectrum, and that in the past there may be some children with C3G who were misclassified with PIGN before C3G was described as a separate disease entity. Children with PIGN (n = 33) diagnosed between 1985 and 2010 who underwent a renal biopsy due to their unusual course were reviewed and of them, 8 were reclassified into C3G based on the current classification criteria. Outcome was based on the degree of proteinuria, C3 level, and renal function at follow-up. Sixteen (72.7%) children with typical PIGN recovered completely as compared to only 2 (25%) with C3G. Of note, children with "typical" PIGN had a more severe disease course at onset; however, the outcome at last follow up was favorable. Our results support the hypothesis that PIGN and C3G form a disease spectrum and have different long-term clinical implications and management strategies.
Hu, Z Y; Chen, Y P; Zha, P
The histopathologic type of 189 cases of chronic glomerulonephritis (GN) were confirmed by renal biopsies, they were subdivided into 3 groups. 77 patients of Western medicine (WM) group was treated by conventional WM (prednison or CTX), and after treatment the total effective rate was 55.8%. The TCM-WM group was treated by the same WM plus treatment according to Syndrome Differentiation with Chinese medicinal herbs, and the total effective rate was 86% in 50 patients. The TCM group was treated by Chinese medicinal herbs, and the total effective rate was 67.3% in 62 cases. There was very significant difference (P < 0.01) between the WM and the TCM-WM group. Among the patients of TCM-WM and TCM groups, 67% of 112 cases were manifested as Dampness-Heat Syndrome, so it suggested that one of the important method for GN treatment is clearing away Dampness-Heat. The effects of TCM-WM group is much better than the WM group in treating mesangio-proliferative GN and membranous GN. It was difficult for WM in treating IgA nephropathy, membrano-proliferative GN and focal glomerulosclerosis, but Chinese medicinal herbs were effective with replenishing Qi and strengthening the Spleen, clearing away Dampness-Heat, promoting blood circulation and relieving Stasis, etc.
Zachwieja, Jacek; Silska, Magdalena; Ostalska-Nowicka, Danuta; Soltysiak, Jolanta; Lipkowska, Katarzyna; Blumczynski, Andrzej; Musielak, Anna
The aim of our study was to analyze the efficacy and safety of rituximab, a chimeric monoclonal antibody against CD20 lymphocytes, as a nonstandard immunosuppressive therapy in children with different types of primary glomerulonephritis who were not eligible for routine treatment. The study group was composed of 16 children with proteinuric glomerulopathies, not responding to standard immunosuppressive therapy. The indications included steroid-resistant nephrotic syndrome (n=14) and steroid-dependent nephrotic syndrome (n=2). The dose of rituximab was established as 375 mg/m2 of body surface area, administered by intravenous infusion once weekly for 1 to 4 weeks, depending on the CD19 lymphocyte count. We evaluated proteinuria and plasma concentration of CD19 lymphocytes at intervals of 1, 3 and 6 months, after which patients received a single repeat dose. Remission, defined as proteinuria less than 150 mg per 24 hours, was observed in 7 of the 16 children. There were no statistically significant differences in leukocyte counts between single and multiple rituximab doses. We also did not observe any clinical or biochemical side effects. In conclusion, we postulate that alternative rituximab therapy should be taken into consideration in nephrotic patients not responding to standard therapy.
Darouich, Sihem; Goucha, Rym; Jaafoura, Mohamed Habib; Zekri, Semy; Kheder, Adel; Ben Maiz, Hédi
Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.
Rossmann, P; Matousovic, K; Bucek, J
In four renal biopsies of two patients with chronic glomerulonephritis (GN), the so-called dense deposit nephropathy (NDD) was diagnosed by means of light, electron, and immunofluorescence microscopy. In routine paraffin sections the picture approached that of the membrano-proliferative GN. In semithin sections (toluidine blue, periodic acid-Ag-methenamine) and especially in the ultrastructure there appeared extensive confluent deposits of a very dense substance, infiltrating the lamina densa of glomerular capillaries, basal membranes of both Bowman's capsules and tubules, and arteriolar walls. In this localization, a non-diffuse "psdudolinear" deposition of beta1c was detected, whereas antisera to main Ig-fractions and fibrin(ogen) were not fixed. In a biopsy performed six years later, a concentration of dense depositis towards the mesangial area and a partial regeneration of basal membranes were observed. In a part of dense deposits there appeared vacuolization, primarily in tubular and arteriolar basal membranes. In glomeruli, focal IgM deposits were apparent at an advanced stage. NDD apparently is a sequel of a particular metabolic (immune?) process, afflicting solely the renal membranous system and distinctly dns known at present. The noncharacteristic clinical presentation resembles chronic. GN, is very protracted, lengthy, and relatively benigh, with a chance of functional and possible even morphological remission.
D'souza, Yvonne B; Jones, Carolyn J P; Short, Colin D; Roberts, Ian S D; Bonshek, Richard E
Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.
Jennette, J C; Tidwell, R R; Geratz, J D; Bing, D H; Falk, R J
Proteases are involved in the pathogenesis of inflammatory diseases by participating in the activation of mediator systems and by producing proteolytic tissue injury. Homeostatic control of inflammation is accomplished in part by physiologic protease inhibitors. The authors investigated the effectiveness of a number of synthetic protease inhibitors in ameliorating the glomerular injury induced by immune complex-mediated glomerulonephritis in mice. Two amidine-type protease inhibitors, bis (5-amidino-2-benzimidazolyl)methane and 1,2-bis (5-amidino-2-benzimidazolyl)ethane, had the greatest effects. They caused a marked reduction in glomerular necrosis (P less than 0.001) but did not affect the amount or site of immune complex localization or leukocyte influx. The inhibition constants of the protease inhibitors against nine purified physiologic proteases were determined. These results were discussed in relation to the effectiveness of the protease inhibitors in reducing glomerular injury. This investigation indicates that the administration of synthetic protease inhibitors can have a beneficial effect on immune-mediated inflammatory injury.
Trascasa, M L; Egido, J; Sancho, J; Hernando, L
Eleven out of 15 patients with IgA mesangial glomerulonephritis (Berger's disease) had an increased proportion of serum IgA in 9-21S fractions on 5-40% sucrose density-gradient ultracentrifugation; the heavier fractions decreased at acid pH. Serum IgA purified by starch electrophoresis was subjected to reduction-alkylation yielding fragments of lower molecular weight. J chain was detected on urea alkaline polyacrylamide electrophoresis and the high-molecular weight IgA bound the human secretory component. In six patients treated with phenytoin for 1 year there was a decrease in polymeric IgA and an increase in monomeric IgA adopting a pattern similar to that of the controls. Our results show the presence of a large amount of true IgA polymers, partially as immune complexes, in the serum of patients with Berger's disease. These data together with their normalization after phenytoin treatment may open a new pathogenic and therapeutic approach to this entity.
Fujita, Y; Inoue, I; Inagi, R; Miyata, T; Shinzato, T; Sugiyama, S; Miyama, A; Maeda, K
FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethane-sulphonate), a potent serine protease inhibitor, has been reported to inhibit complement activity in vitro, and especially the classical complement pathway effectively. In the present study, we examined the inhibitory effect of FUT-175 on the classical complement pathway components by hemolytic assay using purified human complement components. As a result, 50% inhibition of the C1 protease activity for classical C3 convertase formation and for C2 was obtained with 3.0 x 10(-8) M and 7.0 x 10(-8) M of FUT-175, respectively. FUT-175 did not inhibit the C2 protease activity at all. We then administered FUT-175 to 5 glomerulonephritic patients with hypocomplementemia and proteinuria in order to assess the clinical effectiveness of this drug. When FUT-175 was administered intravenously and continuously at a rate of 0.1 to 0.2 mg/kg/hr for 2 weeks, the urinary protein excretion decreased significantly from 2.9 +/- 0.8 to 1.4 +/- 0.5 g/day (P < 0.025). In these patients, some of the serum complement markers (serum C3, C4 level and the hemolytic activity via the classical complement pathway (CH50)) were increased after FUT-175 administration. The above findings suggests that FUT-175 can exert beneficial effects on glomerulonephritis with hypocomplementemia by inhibiting complement activation.
Roberts, J L; Schwartz, M M; Lewis, E J
Although an unusually high incidence of immunological diseases has been described in patients with hereditary C2 deficiency, the severity of these illnesses has been relatively mild, suggesting that blocking complement activation beyond C4 may protect against significant complement-mediated inflammation. This report describes studies in a C2-deficient patient with severe systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis. An immunopathological study of the kidney revealed the deposition of properdin, properdin factor B, C3 and C5 in a pattern similar to immunoglobulin G deposits. Serum properdin and properdin factor B levels were low at various times during the patient's course. In vitro complement fixation studies showed C3 fixation by glomerular deposits could occur via the alternative pathway. Studies of the immune deposits in the patients' skin revealed similar results. These studies suggest that inflammation may be effectively mediated via the alternative complement pathway in the C2 deficiency-lupus syndrome. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 PMID:348363
Góis, Mário; Messias, Ana; Carvalho, Dulce; Carvalho, Fernanda; Sousa, Helena; Sousa, João; Nolasco, Fernando
Renal involvement in rheumatoid arthritis (RA) is common and has a negative impact on patient survival. Only few cases have been reported of necrotizing glomerulonephritis (GN) associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) in patients with RA. We report a patient with RA who developed a necrotizing GN associated with ANCA-MPO, treated with rituximab (RTX). A 55-year-old man with a 27-year history of RA under secukinumab was referred to our nephrology clinic with worsening renal function associated with microhematuria and proteinuria. Our laboratory evaluation showed hypocomplementemia and positive titers for MPO-ANCA (615 U/mL). A renal biopsy demonstrated pauci-immune necrotizing GN. The patient was treated with 3 consecutive pulses of methylprednisolone followed by oral prednisolone (1 mg/Kg) and rituximab (1000 mg, repeated 14 days later). After a 10-month follow-up, the arthritis remains well-controlled, renal function stabilized, proteinuria improved and MPO-ANCA titer normalized (6.3 U/mL). Necrotizing GN is a rare but a serious condition and an early diagnosis is essential to treatment. This is the first case of necrotizing GN (without extra-renal manifestations of vasculitis) in a patient with active RA, successfully treated with RTX.
Pascal, R R; Sian, C S; Brensilver, J M; Kahn, M; Lefavour, G S
It has been postulated that in some patients with obstructive and reflux uropathy proteinuria develops through an intermediate mechanism of immune complex glomerulonephritis involving antigenic material of renal tubular epithelium. A patient with a unilateral ureterocele and nephrotic syndrome underwent bilateral renal biopsies during surgical correction of the obstruction. The obstructed kidney showed mild pyelonephritis, but both kidneys showed a glomerulopathy with electron-dense deposits in the mesangial and paramesangial regions associated with positive immunofluorescence for immunoglobulin M (IgM) and the third component of complement (C3). An IgM antibody was eluted from the biopsy specimens and it reacted by indirect immunofluorescence with normal renal tubular epithelium and with the patient's renal tubular epithelium. The eluate also reacted with pre-eluted glomeruli of the patient, but not with normal glomeruli. All antibody activity could be removed from the eluate by pre-incubation with normal kidney. It is concluded that the unilateral renal obstruction produced tubular injury so that as yet unidentified antigens were recognized by the immune system. The resultant antibody response gave rise to circulating immune complexes which were then deposited in glomeruli with subsequent glomerular damage and nephrotic syndrome.
Donadio, J.V. Jr.; Anderson, C.F.; Mitchell, J.C.; Holley, K.E.; Ilstrup, D.M.; Fuster, V.; Chesebro, J.H.
Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of /sup 51/Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m/sup 2/ of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.
Truong, Luan D; Seshan, Surya V
Membranous glomerulonephritis (MGN) is a very significant kidney disease. It is one of the frequent causes of heavy protein excretion in urine. MGN is thought to be an immune-mediated disease caused by glomerular deposition of antigen-antibody complexes. The pathogenic antigen, however, has been an enigma until recently. It was discovered in 2009 that phospholipase A2 receptor (PLA2R), a normal transmembrane protein in podocyte plasma membrane, is the antigen causing MGN. Within 5 yr of its discovery, this seminal finding has leaded to novel insights into the treatment of this disease including diagnosis, therapy, and prediction of outcome. This finding also paves the way for fundamental studies on how and why autoimmunity against PLA2R develops. The discovery of PLA2A as the cause of "idiopathic" MGN after a half century of speculation, followed by further fundamental insights with such an expedient and successful application in patient care, embodies the elegance of science at its junction with society. This perspective traces the story of this remarkable discovery.
Bob, Flaviu Raul; Gluhovschi, Gheorghe; Herman, Diana; Potencz, Elena; Gluhovschi, Cristina; Trandafirescu, Virginia; Schiller, Adalbert; Petrica, Ligia; Velciov, Silvia; Bozdog, Gheorghe; Vernic, Corina
The aim of this study was to determine the relationship between histological, immunohistochemical (IHC) and biological data in the assessment of interstitial fibrosis in patients with glomerular diseases. A group of 41 patients with primary and secondary glomerulonephritis was studied. In order to quantify the histological changes and to assess the extent of active-inflammatory and chronic-sclerotic/fibrotic interstitial lesions, we adapted a scoring system, initially used for lupus nephritis, and ANCA-associated vasculitis. IHC labeling procedures with monoclonal antibodies anti-smooth muscle actin (SMA), anti-vimentin and anti-transforming growth factor beta (TGFbeta) were assessed using a semi-quantitative score, correlated with the histological and biological data. Our results showed that interstitial labeling of SMA correlated with scores for sclerotic/fibrotic lesions (chronicity index) and with active-inflammatory lesions (interstitial infiltrate, activity index). Interstitial vimentin correlated with the score for interstitial infiltrate. Both interstitial vimentin and TGFbeta immunopositivity correlated with sclerotic/fibrotic lesions (interstitial fibrosis, tubular atrophies, vascular hyalinosis/fibrosis, chronicity index), and negatively with glomerular filtration rate. An important correlation was found between the interstitial labeling of the two IHC markers of myofibroblasts (SMA and vimentin). We conclude that IHC studies related to clinico-biological and histological data can have an important role in the evaluation of the glomerular diseases, but the classical histological investigation assessed through quantification has still not lost its importance.
Wu, Di; Chen, Jin-Song; Cheng, Dong-Rui; Chen, Hao; Li, Xue; Ji, Shu-Ming; Xie, Ke-Nan; Ni, Xue-Feng; Liu, Zhi-Hong; Wen, Ji-Qiu
Proliferative glomerulonephritis with monoclonal IgG deposits manifesting as a nephrotic syndrome recently has been described as a renal disease with the pathological features of mesangial and subendothelial deposits of monoclonal IgG. Eight cases of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after a renal transplant have been reported. Almost all of these patients had a certain remission of proteinuria by steroids alone or with cyclophosphamide, and had further remission through other special treatments (ie, rituximab and plasmapheresis). We present a case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits of the IgG3? subtype after a renal transplant, which was insensitive to pulse intravenous methyl-prednisolone and cyclophosphamide remitted by double filtration plasmapheresis. This case report reveals that recurrent proliferative glomerulo-nephritis with monoclonal IgG deposits may be insensitive to intravenous pulse therapy of methylprednisolone and cyclophosphamide. We advocate double filtration plasmapheresis as an effective treatment of proliferative glomerulo-nephritis with monoclonal IgG deposits on remission of proteinuria.
Resch, M; Banas, B; Endemann, D; Mack, M; Riegger, G A J; Gröne, H J; Krämer, B K
A 15-year-old girl with a history of Kawasaki disease was admitted to our nephrological department due to acute renal failure. Despite antibiotic therapy because of fever and the symptoms of a pharyngitis in the last few days, the girl showed persisting fever and developed arthralgias, an exanthema and a rising serum creatinine as well as anuria. A wide variety of differential diagnoses has to be thought of because of the history of the Kawasaki disease (symptoms like fever, pharyngitis, exanthema and arthralgia), i.e. hemolytic-uremic syndrome, vasculitis, ascending infection, postinfection glomerulonephritis. In consideration of etiologically unclear "rapidly progressive renal failure" with anuria and thrombocytopenia an immediate renal biopsy was done and revealed a severe drug induced acute interstitial nephritis. Due to this diagnosis we treated the patient with corticosteroids. Within 4 weeks serum creatinine declined to 1.8 mg/dl but did not normalize.
Succar, Lena; Boadle, Ross A; Harris, David C; Rangan, Gopala K
Purpose In crescentic glomerulonephritis (CGN), the development of cellular bridges between podocytes and parietal epithelial cells (PECs) triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN. Methods Transmission electron microscopy (TEM) was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN) from day 1 to day 14. Morphometric analysis was conducted on randomly selected glomeruli captured on TEM digital images. Results On day 1 of NSN, there was widespread formation of focal contacts between the cell bodies of neighboring podocytes, and tight junctions were evident at the site of cell-to-cell contact. This was confirmed by the increased expression of the tight junction molecule, zonula occludens-1 (ZO-1), which localized to the points of podocyte cell–cell body contact. On day 2, the interpodocyte distance decreased and the glomerular basement membrane thickness increased. Foot process effacement (FPE) was segmental on day 3 and diffuse by day 5, accompanied by the formation of podocyte cellular bridges with Bowman’s capsule, as confirmed by a decrease in podocyte-to-PEC distance. Fibrinoid necrosis and cellular crescents were evident in all glomeruli by days 7 and 14. In vitro, the exposure of podocytes to macrophage-conditioned media altered cellular morphology and caused an intracellular redistribution of ZO-1. Conclusion The formation of tight junctions between podocytes is an early ultrastructural abnormality in CGN, preceding FPE and podocyte bridge formation and occurring in response to inflammatory injury. Podocyte-to-podocyte tight junction formation may be a compensatory mechanism to maintain the integrity of the glomerular filtration barrier following severe endocapillary injury. PMID:27920570
Pavkovic, Mira; Riefke, Björn; Frisk, Anna-Lena; Gröticke, Ina; Ellinger-Ziegelbauer, Heidrun
MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and thus are involved in various physiological and pathological states. Due to their stability in biofluids miRNAs have also been proposed as biomarkers (BMs) for tissue injury. We investigated the usefulness of urinary miRNAs for detection of site-specific renal damage in an antiglomerular basement membrane glomerulonephritis (GN) model in rats by comparing GN-induced urinary miRNAs profiles to traditional and newer protein BMs, and to proximal tubular injury-induced urinary miRNA profiles observed previously after cisplatin (Cp) treatment. Male Wistar Kyoto and Sprague Dawley rats were dosed once with 1, 2.5, and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. Although serum creatinine and BUN were not changed, several protein BMs and 74 urinary miRNAs were found to be increased 8 and 14 days after NTS administration. Of these 74 miRNAs, 5 were identified as increased after NTS but not after Cp treatment. Using in situ hybridization two of them, miR-10 b and -100, were found to be localized in distal segments of the nephron, potentially reflecting the tubular injury in those regions. Furthermore, evaluation of both miRNA and mRNA expression in the kidney revealed possible miRNA-mRNA interactions mostly associated with fibrotic and transforming growth factor β signaling. In conclusion, our investigations support the potential of urinary miRNAs as specific BMs for kidney injury, and suggest a role of miRNAs in pathological processes during GN in the kidney.
Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku
Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.
Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.
Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429
Takakura, Koji; Mizukami, Kazuhiko; Mitori, Hikaru; Noto, Takahisa; Tomura, Yuichi
While pirfenidone has been established as an effective anti-fibrosis remedy, whether or not its antifibrotic effect contributes to a reduction of proteinuria remains unclear. We investigated the renoprotective properties of pirfenidone in an anti-glomerular basement membrane (GBM) glomerulonephritis model both prophylactically and therapeutically to determine its profile against proteinuria. In the prophylactic regimen, pirfenidone was treated immediately after anti-serum injection. We observed a significant reduction in the progression of proteinuria (P<0.05) and decline in renal function (P<0.01) and also noted histological improvement in renal injury. These effects appeared to be due to the maintained expression of nephrin and podocin on podocytes as well as the reduced expression of profibrotic factors like transforming growth factor-β (TGF-β). The expression of nephrin mRNA was strongly negatively correlated with the amount of urinary protein excretion (R=-0.84, P<0.001), implicating podocyte damage in the outcome of proteinuria (R(2)=0.70). These results suggest that preservation of podocytes with the pirfenidone treatment may have resulted in the decrease of proteinuria. In contrast, when the therapeutic regimen was initiated 2 weeks after nephritis induction, pirfenidone had little effect on the progression of proteinuria, although the decline of renal function and fibrosis were suppressed. Taken together, present findings suggested that pirfenidone prevented the progression of proteinuria only when administered prophylactically but was still able to ameliorate the decline of renal function independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen reduces proteinuria in anti-GBM nephritis via preservation of podocytes with markedly reduced efficacy when administered as a therapeutic regimen.
Aglan, Ahmed; Longen, Sebastian; Dehne, Nathalie; Köhler, Yvette; Hassan, Mohamed; Beck, Martina; Tredup, Claudia; Boosen, Meike; Hsieh, Tzung-Harn Louise; Schaefer, Liliana; Beck, Karl-Friedrich; Pfeilschifter, Josef
Renal mesangial cells are regarded as main players in glomerular inflammatory diseases. To investigate a possible crosstalk between inflammatory and hypoxia-driven signaling processes, we stimulated cultured mouse mesangial cells with different inflammatory agents and analyzed the expression of prolyl hydroxylase domain containing proteins (PHDs), the main regulators of hypoxia-inducible factor (HIF) stability. Administration of IL-1β (1 nM) and TNF-α (1 nM), a combination further referred to as cytokine mix (CM), resulted in a fivefold increase in PHD3 but not PHD1 and PHD2 mRNA expression compared to untreated controls. In contrast, a combination of IL-1β, TNF-α with lipopolysaccharide (10 μg/ml), and interferon-γ (20 ng/ml) designated as CM+ showed a high (60-fold) induction of PHD3 and a moderate (twofold) induction of PHD2 mRNA expression. Interestingly, CM+ but not CM induced the expression of inducible NO synthase and endogenously produced NO was responsible for the immense induction of PHD3 in mesangial cells treated with CM+. We found that CM+ affected PHD3 expression mainly via the NO/HIF axis, whereas PHD3 regulation by CM occurred in a NF-κB-dependent manner. In turn, silencing of PHD3 expression resulted in a decrease in the mRNA expression of ICAM-1, MIP-2, MCP-1, and CXCL-10, which are under control of NF-κB. In a rat model of mesangio-proliferative glomerulonephritis, PHD3 mRNA and protein expression was markedly induced and this effect was nearly abolished when rats were treated with the iNOS-specific inhibitor L-NIL, thus confirming our findings also in vivo.
Soltysiak, Jolanta; Zachwieja, Jacek; Benedyk, Anna; Lewandowska-Stachowiak, Maria; Nowicki, Michal; Ostalska-Nowicka, Danuta
The increase of circulating urokinase plasminogen activator receptor (suPAR) was demonstrated in various diseases showing its prognostic value as well as the link to the inflammatory reaction. In glomerular diseases suPAR was consider to be a causative factor of proteinuria. In present study we aimed to evaluate serum concentration of suPAR in children with primary and secondary glomerulonephritis (GN) and its association with disease severity. The study involved 22 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), 7 with Henoch-Schönlein nephritis (HSN), 7 with lupus nephritis (LN) and 16 controls. Serum suPAR was significantly higher in children with FSGS and LN than controls (respectively: 4.47±1.39 ng/mL vs. 3.23±0.76 ng/mL; p=0.011 and 6.17±1.12 ng/mL vs. 3.23±0.76 ng/mL; p<0.0001). Further, suPAR was increased in LN when compared to FSGS (p=0.031). In the total group suPAR showed negative correlation with eGFR, serum complement C3 and positive with left ventricular mass index. In children with MCD and FSGS the inverse association of suPAR with eGFR was also shown. In children with primary and secondary glomerulonphritis suPAR levels is not associated with proteinuria. In primary GN elevated suPAR levels may result from reduced eGFR reflecting renal damage. In LN, circulating suPAR can be increased further indicating both multi-organ involvement and systemic inflammation reflecting disease severity.
Baikunje, Shashidhar; Vankalakunti, Mahesha; Nikith, A.; Srivatsa, A.; Alva, Suhan; Kamath, Janardhan
Background Crescent formation generally reflects severe glomerular injury. There is sparse literature on post-infectious glomerulonephritis (PIGN) with crescents in adults. This retrospective study looked at nine such cases to see if there is a correlation between the severity of presentation, steroid treatment, histological severity and outcome. Methods Biopsy reports of all the adults who underwent kidney biopsy from February 2010 to June 2014 in a tertiary care hospital were screened and all the cases with the diagnosis of PIGN with crescents were selected. Clinical presentation, laboratory data, histology, treatment and outcome were analysed. Results Six patients had evidence of recent/current infection, but all except two were non-streptococcal. The mean creatinine was 360.67 μmol/L (range 70.72–770.85) and the mean estimated glomerular filtration rate (MDRD eGFR) was 30.28 mL/min/1.73 m2 (range 6.4–111.1) on presentation. All five patients who were treated with steroids had an excellent response. Among the four patients who did not receive steroids, two were left with significant renal impairment (mean MDRD eGFR 23.5 mL/min/1.73 m2) at a mean follow-up of 15.5 months (range 10–21). The mean percentage of glomeruli with crescents was 36.13% (range 11.76–100) and except in one, there was no tubular atrophy or interstitial fibrosis and none had glomerulosclerosis. None of the patients progressed to end-stage renal disease. Conclusion Non-streptococcal infections are more common precipitants. There was no correlation between histological and clinical severity. Patients treated with steroids had better renal outcomes. PMID:26985372
Gupta, Nirupama; Wakefield, Dara N; Clapp, William L; Garin, Eduardo H
Membranoproliferative glomerulonephritis (MPGN type I, II and III) was reclassified in 2013 as MPGN and C3 glomerulopathy (C3G) based on the complement system activation mechanism. To evaluate whether C4d, a component of the classical pathway, could be a diagnostic tool in differentiating between MPGN and C3G. We conducted a retrospective study of 15 MPGN type I, II and III and 13 minimal change disease (MCD) patients diagnosed between 2000 and 2012. C4d staining using the peroxidase method was employed. Using the 2013 C3G consensus classification, the 15 MPGN types I, II and III biopsies were re-classified as MPGN (8) and C3G (7). Following C4d staining, of the 8 biopsies diagnosed as MPGN, 4 had classical pathway involvement [C1q (+), C3 (+), C4d (+)]; two had lectin pathway involvement [C1q (-), C3 (+), C4d (+)]; and, two were reclassified as C3G because the absence of C4d and C1q suggested the presence of the alternative pathway [C1q (-), C3 (+), C4d (-)]. Three of the seven C3G biopsies presented classical pathway involvement and were reclassified as MPGN. The alternative pathway was present in one of the other 4 biopsies considered to be C3G. Two C3G biopsies involved the lectin pathway and the one case of dense deposit disease had lectin pathway involvement. C4d staining may help to differentiate between MPGN and C3G. In addition, the lectin pathway could play a role in the pathogenesis of these glomerulopathies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
Barnes, J. L.; Hastings, R. R.; De la Garza, M. A.
Fibronectin (Fn) regulates cell migration, proliferation, and extracellular matrix formation during embryogenesis, angiogenesis, and wound healing. Fn also promotes mesangial cell migration and proliferation in vitro and contributes to extracellular matrix formation and tissue remodeling during glomerular disease. In this study, we examined, by immunohistochemistry and in situ hybridization, the temporal glomerular localization and cellular sources of Fn in Habu snake venom (HSV)-induced proliferative glomerulonephritis. Early HSV-induced glomerular lesions consisted of microaneurysms devoid of resident glomerular cells and filled with platelets, leukocytes, and erythrocytes. Over the course of the disease, mesangial cells migrated into the lesions, proliferated, and formed a confluent cellular mass. Fn was present in lesions beginning at 8 hours, with highest intensity at 72 hours and diminishing at 2 weeks after HSV. Staining for Fn at 8 and 24 hours after HSV was attributed to platelets and macrophages. In situ hybridization and phenotypic identification of cell types within lesions revealed macrophages as the predominant source of cellular Fn mRNA at these times. At 48 hours after HSV, Fn mRNA was expressed in proliferating mesangial cells in addition to macrophages. Most cells in lesions at 72 hours after HSV were mesangial, at a time when expression of Fn mRNA peaked. Cellular expression for Fn mRNA and translated protein declined at 2 weeks after HSV. These studies support the hypothesis that Fn, derived from platelets and macrophages, provides a provisional matrix involved with mesangial cell migration into glomerular lesions. Fn produced by mesangial cells might contribute to the formation of a stable extracellular matrix. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8080041
Black, Leland L.; Srivastava, Roshni; Schoeb, Trenton R.; Moore, Ray D.; Barnes, Stephen; Kabarowski, Janusz H.
Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue oxidized lipids. However, whether ApoA-I mediates immune suppressive or anti-inflammatory effects in normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from SLE-prone Sle123 mice into normal, ApoA-I knockout (ApoA-I−/−) and ApoA-I transgenic (ApoA-Itg) mice. Increased ApoA-I in ApoA-Itg mice suppressed CD4+ T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor gamma (PPARγ) ligands 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE were increased in lymphocytes of autoimmune ApoA-Itg mice. ApoA-I reduced Th1 cells independently of changes in CD4+FoxP3+ regulatory T cells or CD11c+ dendritic cell activation and migration. Follicular helper T cells, germinal center B cells and autoantibodies were also lower in ApoA-Itg mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have opposite effects on autoimmunity or glomerulonephritis, possibly due to compensatory increases of ApoE on HDL. We conclude that although compensatory mechanisms prevent pro-inflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid PPARγ ligands, and can reduce renal inflammation in glomerulonephritis. PMID:26466956
Bontscho, Julia; Manz, Rudolf A.; Schneider, Wolfgang; Luft, Friedrich C.; Kettritz, Ralph
Anti-neutrophil cytoplasmic autoantibodies (ANCA) cause vasculitis and necrotizing crescentic glomerulonephritis (NCGN). Steroids and cytotoxic drugs reduce mortality but can cause significant adverse events. The proteasome inhibitor bortezomib (BTZ) prevents glomerulonephritis in mouse models of lupus but its efficacy in ANCA-associated glomerulonephritis is unknown. We induced anti-MPO IgG-mediated NCGN by transplanting wild-type bone marrow (BM) into irradiated MPO-deficient mice immunized with MPO. Four weeks after BM transplantation, we treated mice with steroid/cyclophosphamide (S/CYC) or BTZ. Compared with untreated control mice, both S/CYC and BTZ significantly reduced urine abnormalities, NCGN, and infiltration of neutrophils and macrophages. Response to BTZ depended on timing of administration: BTZ abrogated NCGN if begun 3 weeks, but not 5 weeks, after BM transplantation. BTZ treatment significantly reduced total and MPO-specific plasma cells in both the spleen and bone marrow, resulting in significantly reduced anti-MPO titers. Furthermore, BTZ affected neither B cells nor total CD4 and CD8 T cells, including their naive and effector subsets. In contrast, S/CYC reduced the total number of cells in the spleen, including total and MPO-specific plasma cells and B cells. In contrast to BTZ, S/CYC did not affect total and MPO-specific plasma cells in the bone marrow. Three of 23 BTZ-treated mice died within 36 hours after BTZ administration. In summary, BTZ depletes MPO-specific plasma cells, reduces anti-MPO titers, and prevents NCGN in mice. PMID:21233415
Mima, Akira; Abe, Hideharu; Nagai, Kojiro; Arai, Hidenori; Matsubara, Takeshi; Araki, Makoto; Torikoshi, Kazuo; Tominaga, Tatsuya; Iehara, Noriyuki; Fukatsu, Atsushi; Kita, Toru; Doi, Toshio
Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis. PMID:21445358
Cazzato, Massimiliano; Neri, Rossella; Possemato, Niccolo; Puccini, Rodolfo; Bombardieri, Stefano
PFAPA is an acronym for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This syndrome has been usually described in pediatric patients and it generally resolves spontaneously. The endocapillary proliferative glomerulonephritis (EPG) is a glomerular injury characterized by hypercellularity in glomerular lumen and is caused by post-infectious or autoimmune diseases. In this paper, we describe the case of a 35-year-old man affected by PFAPA and EPG. To our knowledge this association has never been reported in the literature before.
Konstantinov, Konstantin N; Harris, Alexis A; Barry, Marc; Murata, Glen H; Tzamaloukas, Antonios H
A woman diagnosed with mixed connective tissue disease (MCTD) developed an anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) and nephrotic syndrome with normal serum creatinine. Percutaneous kidney biopsy showed pauci-immune glomerulonephritis with superimposed immune complex deposition. After treatment with cyclophophamide and prednisone, proteinuria decreased progressively to a level of 0.4 g/g creatinine, ANCA became undetectable, while serum creatinine remained normal seven years after the beginning of treatment. Sustained remission of nephrotic proteinuria with preserved renal function may follow treatment of ANCA-mediated disease developing in patients with MCTD.
Stills, H. F.; Bullock, B. C.; Clarkson, T. B.
A study was conducted to compare the effects of experimental immune complex disease on the development of glomerulonephritis and aortic and coronary artery atherosclerosis. Fourteen adult male macaques (Macaca fascicularis) were fed a mildly atherogenic diet. Ten of these animals were given repeated intravenous injections of bovine serum albumin (BSA), and the remaining 4 were given similar injections of saline. Three of the monkeys given BSA responded with a high antibody titer, 4 with a moderate titer, and 3 with a low level titer to BSA. In all 4 monkeys with the moderate antibody response glomerulonephritis developed, characterized by increased glomerular cellularity, electron-dense deposits in the glomerular capillary basal lamina, and deposits of IgG, IgM, C3, C4, and BSA. Glomerulonephritis was not seen in the other 6 monkeys given BSA or the 4 control monkeys. Aortic lesions seen at necropsy consisted of a few fatty intimal streaks with no differences between test monkeys (given BSA) and control monkeys (given saline). There was no correlation between total serum cholesterol concentration, high-density lipoprotein cholesterol concentration, or BSA antibody levels and the degree of aortic atherosclerosis. Immunochemical stains for immunoglobulins and complement components revealed increased intimal staining when intimal thickness increased. Medial staining for immunoglobulin and complement components appeared to be slightly increased in monkeys with moderately high-level titers of BSA. The extent of atherosclerosis in the coronary arteries of monkeys given BSA was greater than in the control animals. Differences in the extent and severity of the atherosclerotic lesions were most pronounced in the proximal portions of the main coronary arteries, suggesting an increased susceptibility of this site to immune-complex-exacerbated atherosclerosis. In addition to the increased lesion severity in monkeys given BSA, there were numerous granulocytes seen within
Pepper, Ruth J; Wang, Hsu-Han; Rajakaruna, Gayathri K; Papakrivopoulou, Eugenia; Vogl, Thomas; Pusey, Charles D; Cook, H Terence; Salama, Alan D
Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9(-/-)), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow-derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14(-/-) cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow-derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14(-/-) bone marrow-derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow-derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis.
Pepper, Ruth J.; Wang, Hsu-Han; Rajakaruna, Gayathri K.; Papakrivopoulou, Eugenia; Vogl, Thomas; Pusey, Charles D.; Cook, H. Terence; Salama, Alan D.
Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9−/−), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow–derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14−/− cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow–derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14−/− bone marrow–derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow–derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis. PMID:25759267
Yang, Jihyun; Seo, Min Young; Kim, Ki Tae; Lee, Jun Yong; Kim, Sun-Chul; Kim, Myung-gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu; Won, Nam Hee; Cha, Ran-Hui; Cho, Eunjung
Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed “lupus-like feature” glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding. PMID:25120835
Esposito, Susanna; Bianchini, Sonia; Fastiggi, Michele; Fumagalli, Monica; Andreozzi, Laura; Rigante, Donato
Group A Streptococcus (GAS) strains are lately classified on the basis of sequence variations in the emm gene encoding the M protein, but despite the high number of distinct emm genotypes, the spectrum of phenotypes varying from invasive suppurative to non-suppurative GAS-related disorders has still to be defined. The relationship of GAS types with the uprising of acute rheumatic fever (ARF), a multisystemic disease caused by misdirected anti-GAS response in predisposed people, is also obscure. Studies published over the last 15 years were retrieved from PubMed using the keywords: "Streptococcus pyogenes" or "group A Streptococcus" and "acute rheumatic fever": the prevalence of peculiar emm types across different countries of the world is highly variable, depending on research designs, year of observation, country involved, patients' age, and gender. Most studies revealed that a relatively small number of specific emm/M protein types can be considered "rheumatogenic", as potentially characterized by the possibility of inducing ARF, with remarkable differences between developing and developed countries. The association between emm types and post-streptococcal manifestations is challenging, however surveillance of disease-causing variants in a specific community with high rate of ARF should be reinforced with the final goal of developing a potential primary prophylaxis against GAS infections.
Bauer, Eva; Schlederer, Michaela; Scheicher, Ruth; Horvath, Jaqueline; Aigner, Petra; Schiefer, Ana-Iris; Kain, Renate; Regele, Heinz; Hoermann, Gregor; Steiner, Günter; Kenner, Lukas; Sexl, Veronika; Villunger, Andreas; Moriggl, Richard; Stoiber, Dagmar
The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity. PMID:26919255
Bataille, Stanislas; Kaplanski, Gilles; Boucraut, José; Halfon, Philippe; Camus, Claire; Daniel, Laurent; Burtey, Stéphane; Berland, Yvon; Dussol, Bertrand
We report on 3 cases of membranoproliferative glomerulonephritis associated with mixed cryoglobulin in patients with hepatitis C virus (HCV) antibodies but a negative blood viral load. These cases explore the pathogenesis of the renal disease. We searched for occult HCV infection in peripheral blood mononuclear cells, cryoprecipitate, bone marrow cells, and glomeruli using ultrasensitive PCR assays and immunohistochemistry. We also looked for infraclinical B cell lymphoma by computed tomodensitometry, bone marrow aspiration and biopsy, and lymphocyte typing. By PCR assays, we did not evidence occult hepatitis C infection in peripheral blood mononuclear cells, bone marrow cells, or cryoprecipitates. In the only patient with available kidney specimen, we evidenced HCV-NS3 antigen in glomeruli. HCV-associated lymphoma was excluded, but mild polyclonal B lymphocytosis was present in the 3 patients. Remission occurred spontaneously in 1 patient, and in another patient it occurred after rituximab treatment. The third patient was lost to follow-up. In patients with hepatitis C-negative viral load, membranoproliferative glomerulonephritis could be induced by the persistence of HCV antigen in the kidney but not in hematopoietic cells. Nonlymphomatous B cell proliferation may also be induced by chronic viral stimulation. Copyright © 2012 S. Karger AG, Basel.
Okpechi, Ikechi G.; Ameh, Oluwatoyin I.; Bello, Aminu K.; Ronco, Pierre; Swanepoel, Charles R.; Kengne, Andre P.
Background and aim Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. Materials and methods We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. Results Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50–4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2–22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3–21.1), mesangiocapillary GN (MCGN); 11.8% (9.2–14.6), crescentic GN; 2.0% (0.9–3.5) and IgA nephropathy 2.8% (1.3–4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0–18.4) and 7.7% (4.5–11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. Conclusions Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases
Okpechi, Ikechi G; Ameh, Oluwatoyin I; Bello, Aminu K; Ronco, Pierre; Swanepoel, Charles R; Kengne, Andre P
Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50-4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2-22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3-21.1), mesangiocapillary GN (MCGN); 11.8% (9.2-14.6), crescentic GN; 2.0% (0.9-3.5) and IgA nephropathy 2.8% (1.3-4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0-18.4) and 7.7% (4.5-11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases; this could have a positive impact on chronic kidney disease evaluation and
Tang, W W; Feng, L; Vannice, J L; Wilson, C B
The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in
Idasiak-Piechocka, I; Oko, A; Łochyńska, K; Woźniak, A; Czekalski, S
Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in
Oliveira, A. V.; Roque-Barreira, M. C.; Sartori, A.; Campos-Neto, A.; Rossi, M. A.
likely that they are implicated in the pathogenesis of the mesangial proliferative glomerulonephritis in hamsters experimentally infected with L donovani. The glomerular changes may also explain the loss of immunoglobulins in the urine and the consequent lowering of serum immunoglobulin levels. Images Figure 2 Figure 3 Figure 4 PMID:4025511
Ferluga, D; Jerse, M; Vizjak, A; Hvala, A; Rozman, B; Kos-Golja, M; Bren, A F
In addition to the conventional World Health Organization (WHO) classification of lupus glomerulonephritis (GN), various concomitant approaches have been introduced in the evaluation of renal biopsies of patients with systemic lupus erythematosus (SLE) in order to increase the impact of biopsies on the decision concerning the most appropriate therapy as well as for establishing the prognosis. Three hundred and seventy kidney tissue samples from 267 SLE patients were analysed using standardised light, electron and immunofluorescence microscopic techniques. In 155 patients, a comparative clinical follow-up study and statistical analysis were performed. The study highlighted the heterogeneity of WHO classes IV and III, which include 5 and 6 different conventional histomorphologic types of GN, respectively. Mixed membranous and proliferative GN associated with "full-house" mesangial-transmembranous immune deposits, demonstrated in more than one third of our SLE cases, appears to be diagnostically most characteristic. Immune deposits distributed in the glomeruli in five different patterns, obviously play a major role in the pathogenesis of various WHO classes and histomorphologic types of lupus GN. Additional mechanisms related to the occurrence of antiphospholipid antibodies and antineutrophil cytoplasmic antibodies are suggested to contribute to the histomorphologic heterogeneity of WHO class III and IV lupus GN, particularly to the development of thrombotic, necrotising and crescentic glomerular lesions. In the present study, a statistically significant association was demonstrated between increasing mean values of the activity index and glomerular deposit distribution patterns labeled by subendothelial deposits. Furthermore, a significant correlation was established between an increasing risk of developing renal failure and increasing mean values of the chronicity index. Differences in the increasing risk of developing renal failure between groups with different
Graham, D I; Behan, P O; More, I A
The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney. Images PMID:762582
Starczewska, Małgorzata H; Wawrzyńska, Liliana; Opoka, Lucyna; Małek, Grzegorz; Wieliczko, Monika; Amatuszkiewicz-Rowińska, Joanna; Szturmowicz, Monika
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that is characterized by its chronic course and the involvement of many organs and systems. The most common abnormality in the respiratory system of SLE patients is lupus pleuritis. Less common is parenchymal involvement, which may present as acute lupus pneumonitis (ALP) or chronic interstitial lung disease. Other possible pulmonary manifestations of SLE include pulmonary embolism, diffuse alveolar haemorrhage, acute reversible hypoxaemia, and shrinking lung syndrome. We present the case report of a young woman with previously diagnosed membranous glomerulonephritis with nephrotic syndrome and antiphospholipid syndrome, who was admitted with marked of shortness of breath. The diagnostic process, including imaging studies and laboratory tests, enabled us to confirm a diagnosis of ALP. After initiation of treatment with high doses of methyloprednisolone, nearly complete remission of pulmonary changes was observed. We also perform a literature review regarding acute lupus pneumonitis.
Samuel, Susan; Bitzan, Martin; Zappitelli, Michael; Dart, Allison; Mammen, Cherry; Pinsk, Maury; Cybulsky, Andrey V; Walsh, Michael; Knoll, Greg; Hladunewich, Michelle; Bargman, Joanne; Reich, Heather; Humar, Atul; Muirhead, Norman
The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of pediatric nephrologists reviewed the guideline statements for management of childhood nephrotic syndrome and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas in which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the length of corticosteroid therapy for the initial presentation and relapses, definitions of steroid resistance, and choice of second-line agents, are discussed in more detail. Existing practice variation is also addressed.
Peces, R; Rodríguez, M; Pobes, A; Seco, M
We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 67-year-old woman with diabetes. Intensive combined immunosuppressive therapy with methylprednisolone bolus, oral prednisone, and cyclophosphamide led to negativity of anti-GBM antibodies but was not able to restore renal function. After 28 months of hemodialysis, the patient suddenly presented with pulmonary hemorrhage. In this setting, high levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and negative anti-GBM antibodies were found. Therapy with oral prednisone and cyclophosphamide led to resolution of pulmonary hemorrhage and negativity of MPO-ANCA.
Zeman, Marilyn; Campbell, Patricia; Bain, Vincent G
Postrenal transplant hepatitis C is increasing in frequency due to the high prevalence of hepatitis C among patients with renal failure. Despite this, there is still no standard hepatitis C treatment available for renal transplanted recipients. Combination antiviral hepatitis C therapy, the standard of care in the nontransplant population, is generally avoided because of documented renal graft rejection secondary to interferon treatment. A case of a male patient with postrenal transplant hepatitis C, which was associated with cryoglobulinemia and glomerulonephritis of the graft, is presented. He was treated with standard interferon with ribavirin. Sustained viral clearance was achieved despite ongoing evidence of cryoglobulinemia. Renal function, which had been deteriorating before treatment, improved as evidenced by the stabilization of serum creatinine and marked improvement of proteinuria. In conclusion, in selected patients, combination antiviral therapy may still be a viable option postrenal transplant. PMID:16779461
Watanabe, S; Yamaguchi, Y; Suzuki, T; Ikezoe, M; Matsumoto, N; Chikamoto, H; Nagafuchi, H; Horita, S; Hattori, M; Shiraga, H; Tokumoto, T; Tanabe, K; Toma, H; Ito, K
A 38-yr-old man with factor H dysfunction and unknown glomerular disease received first and second renal transplantations (Tx) from living-related donors. His examination showed a low percentage activity of factor H (31%). Factor H dysfunction has been known to be associated with type II or III membranoproliferative glomerulonephritis (MPGN), haemolytic uraemic syndrome and IgA GN. The first graft from his mother showed diffuse mesangial deposit of IgA. His son has had IgA GN and his data also revealed a low percentage activity of factor H (33%). He and his son both showed a low activity of C3. Moreover, his father, who was the donor of the second Tx, had a low percentage activity of factor H (25%), and presented with mild glomerular deposit of C3 at operation, while he has been healthy through his entire 67 yr of life. Each of them had a low percentage activity of factor H. These findings through three generations suggested the inheritance of factor H dysfunction. The patient presented with proteinuria 3 months after the first Tx. At the first biopsy 30 months after the first Tx, light microscopy revealed minor glomerular abnormalities with electron dense deposits in subepithelial, intramembranous and mesangial regions, while immunofluorescence showed massive glomerular deposits of C3. In the second biopsy 51 months after the first Tx, the glomerulonephritis developed mesangial proliferation and crescent formation, accompanied by more massive C3 deposit and intramembranous, mesangial and subepithelial dense deposits. He then required redialysis. At the second and third biopsies within 2 months after the second Tx, the renal graft showed similar findings to the first biopsy after the first Tx. He perhaps presented with a recurrence of complement-associated GN, showing an atypical form of MPGN after Tx. These findings suggest that factor H dysfunction may play an important role of a certain pathogenesis of GN.
Yu, Tung-Min; Wen, Mei-Chin; Wu, Ming-Ju; Chen, Cheng-Hsu; Cheng, Chi-Hung; Li, Chi-Yuan; Shu, Kuo-Hsiung
Successful renal transplantation has been performed in patients with end-stage renal disease and has been routine in patients with end-stage renal failure for more than two decades. Despite advances in the use of immunosuppressants, there has been only modest improvement in long-term allograft survival. Accumulating data have demonstrated that chronic rejection and recurrent glomerulonephritis are major causes of long-term allograft loss. However, data regarding the long-term impact of posttransplantation glomerulonephritis (PTGN) on ethnic Chinese populations are still unavailable. From 1984 to 2010, a total of 268 patients who underwent renal allograft biopsies were reviewed retrospectively. Renal outcomes were compared by Kaplan-Meier analysis, and risk factors for renal survival and all-cause mortality were analyzed using the Cox proportional hazards model. In all, 85 patients (31.7%) had PTGN, and the mean time of disease onset was 5.32±5.18 years after transplantation. Among the 85 PTGN cases, 33 (39%) were immunoglobulin A (IgA) nephropathy, 24 (28%) were focal segmental glomerulosclerosis, and 8 (9.4%) were membranous GN. Significant risk was associated with posttransplant IgA GN in hepatitis B virus carriers (odds ratio 5.371, 95% confidence interval 1.68, 17.19; p=0.0064). A total of 45 PTGN patients had allograft loss, of whom 49% had IgA nephropathy. Patients with PTGN had inferior allograft survival rates compared to those with other pathologic findings (p<0.0003). Taken together, our results indicate that PTGN had a strong negative impact on long-term kidney graft survival. Posttransplant IgA nephropathy is a leading cause of allograft loss in Chinese kidney transplant patients with PTGN.
Shah, Shivani; Havill, John; Rahman, M Hafizur; Geetha, Duvuru
Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of ANCA-associated vasculitis. The lack of ANCA antibodies may indicate a variation in clinical presentation and outcomes of this disease. We identified 74 adult patients between 1995 and 2009 with the diagnosis of pauci-immune glomerulonephritis. Demographics, histological features, and treatment outcomes were compared between ANCA-positive and ANCA-negative patients. These factors were correlated with renal function at presentation and follow-up. Of the 74 patients, 57 were ANCA-positive, and 17 were ANCA-negative. Demographics and mean Birmingham Vasculitis Activity Score were similar between ANCA-negative and ANCA-positive patients at presentation. Renal function was significantly worse at presentation in the ANCA-negative patients (eGFR 16.59 vs. 31.89 ml/min/1.73 m(2), p = 0.03). Patients in the ANCA-negative group had a significantly higher interstitial fibrosis score compared to the ANCA-positive group (2.1 vs.1.6, p = 0.04). The median time to remission was shorter in the ANCA-negative patients (51 vs. 78 days, p = 0.01). Long-term renal function and 1-year patient and renal survival were similar between ANCA-negative and ANCA-positive patients. Baseline eGFR, percentage of normal glomeruli, glomerular sclerosis, and tubulointerstitial scarring predicted eGFR at 1 year in both groups similarly. This is the first historical review of American patients with pauci-immune glomerulonephritis, comparing patients with ANCA-negative and ANCA-positive serology. Although ANCA-negative patients present with lower eGFR and more interstitial fibrosis, 1-year and long-term outcomes in both groups are similar.
Higuchi, N; Maruyama, H; Kuroda, T; Kameda, S; Iino, N; Kawachi, H; Nishikawa, Y; Hanawa, H; Tahara, H; Miyazaki, J; Gejyo, F
Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4+ T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.
Nitsche-Schmitz, D Patric; Chhatwal, Gursharan S
Otherwise uncomplicated infections with Streptococcus pyogenes can cause two insidious immune sequelae known as post-streptococcal glomerulonephritis (PSGN) and acute rheumatic fever (ARF). These diseases follow with a latency of a few weeks or months after primary infection and are responsible for high mortality and morbidity. PSGN has also been linked to infections with group C streptococci of the species S. equi ssp. zooepidemicus (SESZ). Moreover, there are some indications that infection with group C and G streptococci (GCGS) of the subspecies Streptococcus dysgalactiae ssp. equisimilis (SDSE) leads to ARF. Despite decades of research, the picture of the molecular pathogenesis of streptococcal immune sequelae resembles a jigsaw puzzle. Herein we try to put some of the puzzle bits together that have been collected till date.
[Hypocomplementary membrano-proliferative glomerulonephritis in a Malagasy patient with schistosomiasis mansoni (detection of bilharzial antigen on glomerular basement membrane using monoclonal antibodies)].
Rajaonarivelo, P; Rajaona, H R; Alix, J L; Couderc, P; Daveau, C; Santoro, F; Nogueira-Quetroz, J A; Lovens, M; Capron, A; Cordonnier, D
Schistosomiasis due to Schistosoma mansoni affects more than 40 millions people all over the world. Renal involvement is observed mainly in endemic areas. We report a case of hypocomplementemic membrano-proliferative glomerulonephritis in a malagasy man who suffered also from hepatosplenic bilharziosis. The relation between Schistosoma mansoni and the nephropathy was proved by indirect immunofluorescence test using a monoclonal antibody directed against the caecum of adult Schistosoma mansoni.
Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E.; Borza, Dorin-Bogdan
The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport post-transplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM antibodies. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to antibody-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 cross-links, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys—a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by post-translational modifications of an autoantigen. PMID:20709951
Suzuki, Eiji; Karam, Eva; Williams, Sarah; Watson, Dennis K; Gilkeson, Gary; Zhang, Xian K
Expression of transcription factor Fli-1 is implicated in the development of glomerulonephritis. Fli-1 heterozygous knockout (Fli1(+/-)) NZM2410 mice, a murine model of lupus, had significantly improved survival and reduced glomerulonephritis. In this study, we found that infiltrated inflammatory cells were significantly decreased in the kidneys from Fli-1(+/-) NZM2410 mice. The expression of monocyte chemoattractant protein-1 (MCP-1) was significantly decreased in kidneys from Fli-1(+/-) NZM2410 mice. The primary endothelial cells isolated from the kidneys of Fli-1(+/-) NZM2410 mice produced significantly less MCP-1. In endothelial cells transfected with specific Fli-1 siRNA the production of MCP-1 was significantly reduced compared to cells transfected with negative control siRNA. By Chromatin Immunoprecipitation (ChIP) assay, we further demonstrated that Fli-1 directly binds to the promoter of the MCP-1 gene. Our data indicate that Fli-1 impacts glomerulonephritis development by regulating expression of inflammatory chemokine MCP-1 and inflammatory cell infiltration in the kidneys in the NZM2410 mice. Published by Elsevier Inc.
Mavani, Gaurang P; Pommier, Max; Win, Sandar; Michelis, Michael F; Rosenstock, Jordan
A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 μmol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative glomerulonephritis most likely due to ANCA vasculitis. He received three doses of pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U (normal <1). He was started on high-dose oral steroids; monthly intravenous cyclophosphamide and plasmapheresis were also initiated. His symptoms improved and creatinine is 247.5 μmol/L (2.8 mg/dL). His repeat anti-GBM antibody was negative. This is a rare case of rapidly progressive glomerulonephritis due to dual MPO-ANCA antibodies and anti-GBM antibodies (DAV).
Mavani, Gaurang P.; Pommier, Max; Win, Sandar; Michelis, Michael F.; Rosenstock, Jordan
A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 μmol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative glomerulonephritis most likely due to ANCA vasculitis. He received three doses of pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U (normal <1). He was started on high-dose oral steroids; monthly intravenous cyclophosphamide and plasmapheresis were also initiated. His symptoms improved and creatinine is 247.5 μmol/L (2.8 mg/dL). His repeat anti-GBM antibody was negative. This is a rare case of rapidly progressive glomerulonephritis due to dual MPO-ANCA antibodies and anti-GBM antibodies (DAV). PMID:26301224
Jonsson, C A; Svensson, L; Carlsten, H
The aim of the present study was to evaluate the therapeutic effect of mycophenolate mofetil (MMF) on the course of disease in SLE-prone MRLlpr/lpr mice. Three-months-old mice displaying clinical symptoms of glomerulonephritis were given MMF (100 mg/kg per day) orally via the drinking water. Control mice received i.p. injections of cyclophosphamide (CYC) (1.8 mg/mouse per week) or saline. Survival, albuminuria and haematuria, immunoglobulin levels and anti-dsDNA antibodies in serum, frequencies of immunoglobulin-producing B lymphocytes and glomerular deposits of immunoglobulin and C3 were analysed. The results showed that MMF treatment significantly prolonged survival and reduced the occurrence of albuminuria and haematuria in MRLlpr/lpr mice. In addition, the number of immunoglobulin-producing B cells and serum levels of IgG and IgG anti-dsDNA antibodies were reduced after MMF and CYC treatment. MMF treatment significantly reduced the extent of deposition of C3 in glomeruli. We conclude that the reduced severity of glomerulonephritis following treatment of lupus-prone mice with MMF was as efficacious as that of CYC. These results warrant clinical trials of MMF in SLE patients with glomerulonephritis. PMID:10361247
Introduction Autosomal dominant polycystic kidney disease is an inherited disorder that is characterized by the development and growth of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/24 hours in autosomal dominant polycystic kidney disease, and an association of nephrotic syndrome with this condition is considered rare. There are only anecdotal case reports of autosomal dominant polycystic kidney disease associated with nephrotic syndrome, with focal segmental glomerulosclerosis being the most commonly reported histopathological diagnosis. Nephrotic-range proteinuria in the presence of autosomal dominant polycystic kidney disease, with or without an accompanying decline in renal function, should be investigated by open renal biopsy to exclude coexisting glomerular disease. To the best of our knowledge, this is the first case of autosomal dominant polycystic kidney disease with histologically proven diffuse proliferative glomerulonephritis presenting with nephrotic-range proteinuria. No other reports of this could be found in a global electronic search of the literature. Case presentation We report the case of a 35-year-old Indo-Aryan man with autosomal dominant polycystic kidney disease associated with nephrotic syndrome and a concomitant decline in his glomerular filtration rate. Open renal biopsy revealed diffuse proliferative glomerulonephritis. An accurate diagnosis enabled us to manage him conservatively with a successful outcome, without the use of corticosteroid which is the standard treatment and the drug most commonly used to treat nephrotic syndrome empirically. Conclusion Despite the reluctance of physicians to carry out a renal biopsy on patients with autosomal dominant polycystic kidney disease, our case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria to make an accurate diagnosis. It also illustrates the importance of open renal
Giannico, Giovanna A; Arnold, Shanna; Langone, Anthony; Schaefer, Heidi; Helderman, J Harold; Shaffer, David; Fogo, Agnes B
We have observed a predominantly mesangial non-immunoglobulin A immune complex mesangial glomerulopathy (MG) in renal transplants with mesangial deposits by immunofluorescence and electron microscopy. Clinicopathological features of 28 patients with MG were analyzed and compared with 28 transplant controls, matched for age, sex, ethnicity, donor type, estimated glomerular filtration rate, and interval from transplant to biopsy. Indications for biopsy in the MG group were allograft dysfunction in 64%, allograft dysfunction/proteinuria in 29%, and proteinuria in 7%. Biopsy indications in controls were allograft dysfunction (61%), allograft dysfunction/proteinuria (18%), proteinuria (14%), and delayed graft function (7%). Most MG cases had mild mesangial hypercellularity with endocapillary proliferation in 2 and crescents in 2 without fibrinoid necrosis. Immunoglobulin M-dominant deposits were present in 83%, and immunoglobulin G was dominant in 17% with mesangial deposits in 93% of cases by electron microscopy. Compared with controls, MG had higher Banff interstitial inflammation score (i) (P = .036) and was associated with concurrent acute T-cell-mediated rejection (P = .023), but not with acute or chronic antibody-mediated rejection. MG patients and controls had similar prevalence of polyomavirus nephropathy and Epstein-Barr virus infection. At follow-up, most MG patients had stable estimated glomerular filtration rate with no or stable proteinuria. Disease-specific graft survival was not different in MG versus controls. We conclude that, in view of the apparent self-limited nature of this lesion, additional treatment may not be required in these patients. Awareness of this lesion may thus spare patients unwarranted further intervention.
Mukhin, I V
Renal fibronectin synthesis is impaired in patients with chronic glomerulonephritis. We measured urinary fibronectin for evaluating the efficiency of various methods of treatment. Traditional therapy of patients with the nephrotic syndrome at the stage of renal failure leads to decrease of fibronectinuria, which can be indicative of the progress of nephrosclerotic process in the renal parenchyma; monotherapy with wobenzyme during the azothemic stage of disease in patients with the urinary and nephrotic syndrome does not cause statistically significant changes in the level of urinary fibronectin, which can be regarded as inhibition of nephrosclerosis process. Hence, wobenzyme is the drug of choice, decreasing the velocity of nephrosclerotic processes, when pathogenetic therapy is largely limited or precluded. Combination of wobenzyme with pathogenetic drugs in patients with the nephrotic syndrome and intact renal function suppresses fibronectinuria due to mutual potentiation of the antiinflammatory effect. Decrease of fibronectin concentration in the urine after wobenzyme monotherapy in patients with the urinary syndrome without signs of chronic renal insufficiency confirms the antiinflammatory effect of the drug.
Sui, Weiguo; Li, Huan; Ou, Minglin; Tang, Dong'e; Dai, Yong
Mesangial proliferative glomerulonephritis (MsPGN) is one of the most common immune-mediated renal diseases. The mesangium is expanded and hypercellular, immuno-globulin deposits can be found in the mesangium, but the mechanism underlying its cause remains largely unclear. There is a large amount of evidence suggesting that long ﹥200 nucleotide) non-coding RNAs (lncRNA) have important regulatory functions in the epigenetic control of gene expression. Multiple lines of evidence increasingly link mutations and dysregulations of lncRNAs to a diverse number of human diseases. Through microarray expression analysis, tests show that thousands of lncRNAs and protein-coding genes are significantly differentially expressed in IgA-negative MsPGN. Some lncRNAs and their neighboring protein-coding genes are closely related and are cooperatively expressed. This may be part of a potential regulatory mechanism. The malfunction of regulation in the network of lncRNAs may be a possible mechanism for the development of IgA-negative MsPGN. Our observations suggest that some lncRNAs are closely related to IgA-negative MsPGN and may be playing an important role in this disease.
Multiple studies have identified CD4+ T cells as central players of glomerulonephritis (GN). Cells of the Th1 and Th17 responses cause renal tissue damage, while Tregs mediate protection. Recently, a high degree of plasticity among these T cell lineages was proposed. During inflammation, Th17 cells were shown to have the potential of transdifferentiation into Th1, Th2, or alternatively anti-inflammatory Tr1 cells. Currently available data from studies in GN, however, do not indicate relevant Th17 to Th1 or Th2 conversion, leaving the Th17 cell fate enigmatic. Tregs, on the other hand, were speculated to transdifferentiate into Th17 cells. Again, data from GN do not support this concept. Rather, it seems that previously unrecognized subspecialized effector Treg lineages exist. These include Th1 specific Treg1 as well as Th17 directed Treg17 cells. Furthermore, a bifunctional Treg subpopulation was recently identified in GN, which secrets IL-17 and coexpresses Foxp3 together with the Th17 characteristic transcription factor RORγt. Similarities between these different and highly specialized effector Treg subpopulations with the corresponding T helper effector cell lineages might have resulted in previous misinterpretation as Treg transdifferentiation. In summary, Th17 cells have a relatively stable phenotype during GN, while, in the case of Tregs, currently available data suggest lineage heterogeneity rather than plasticity. PMID:27974866
Yamaguchi-Yamada, Misuzu; Manabe, Noboru; Uchio-Yamada, Kozue; Akashi, Naotsugu; Goto, Yasufumi; Miyamoto, Youhei; Nagao, Masaya; Yamamoto, Yoshie; Ogura, Atsuo; Miyamoto, Hajime
The ICR-derived glomerulonephritis (ICGN) mouse, a new inbred mouse strain with a hereditary nephrotic syndrome, is considered to be a good model of human idiopathic nephrotic syndrome and notably exhibits proteinuria and hypoproteinemia from the neonatal stage. In chronic renal disorder (CRD), anemia is a major subsequent symptom (renal anemia). The precise cause of renal anemia remains unclear, primarily owing to the lack of appropriate spontaneous animal models for CRD. To establish adequate animal models for anemia with CRD, we examined the hematological-biochemical properties and histopathological characteristics. With the deterioration of renal function, ICGN mice developed a normochromic and normocytic anemia, and exhibited normochromic and microcytic at the terminal stage. The expression of erythropoietin (EPO) mRNA both in the kidneys and liver and the EPO leak into the urine were observed in ICGN mice, indicating a disrupted metabolism of EPO in ICGN mice. In addition, a lack of iron induced by the hemolysis in the spleen and the leak of transferrin into urine as proteinuria aggravated the anemic condition. In conclusion, the ICGN mouse is a good model for anemia with CRD.
Hamano, Yoshitomo; Yoshizawa, Hiromichi; Sugase, Taro; Miki, Takuya; Ohtani, Naoko; Hanawa, Shiho; Takeshima, Eri; Morishita, Yoshiyuki; Saito, Osamu; Takemoto, Fumi; Muto, Shigeaki; Yumura, Wako; Kusano, Eiji
We report the case of a 36-year-old Japanese woman with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) Type I diagnosed after a 5-year history of periodic fever syndrome (PFS). Hypocomplementemia and elevation of anti-proteinase 3 anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) were observed. HIV, and hepatitis B and C serology were negative. Nephrotic syndrome and periodic fever did not respond to oral steroid and intravenous steroid pulse therapies combined with cyclosporine, dipyridamole, warfarin and losartan. We tried immunotherapy using rituximab, a human-mouse chimeric monoclonal antibody directed against the CD20 antigen on mature B cells. This therapeutic approach led to improvement of renal function and remission of nephrotic syndrome and hypocomplementemia. However, it did not have a beneficial effect on periodic fever. Suspecting adult-onset hereditary PFS, we analyzed her genetic alteration of MEFV and TNFRSF1A genes. A rare genotype in intron 6 of TNFRSF1A was revealed. The etiological relationship between periodic fever and MPGN is discussed. Rituximab is a hopeful choice of induction therapy for refractory MPGN. PMID:23197963
Hara, Masaki; Nemoto, Tetsuo; Hijima, Tsunekazu; Tsuchiya, Ken; Nitta, Kosaku; Ando, Minoru
A 53-year-old Japanese male was diagnosed with atopic dermatitis and initiated treatment with a local dermatologist in February 2001. A routine medical check-up revealed proteinuria, microscopic hematuria and slight elevation of serum creatinine level in spring 2006. He was referred to our hospital for nephrology consultation and followup.In December 2009, he developed a sudden high fever of greater than 39 °C with sore throat. In addition, his serum creatinine level greatly increased to 4.6 mg/dl. His prevalent renal illness was thought to be rapidly progressive glomerulonephritis (RPGN). Soon after admission, kidney and skin biopsies were performed. The kidney specimens showed that the glomeruli had proliferative mesangial cells strongly positive for anti-IgA antibody, 75% of which manifested fibrocellular crescentic formation surrounding the Bowman's capsules. His skin disease was pathologically proven to be mycosis fungoides(MF). It is likely that his kidney disease was exacerbated by the upper respiratory tract infection and converted to RPGN. Ash is kidney function rapidly declined, hemodialysis therapy was initiated and he remains on chronic dialysis therapy. This is a serious case of IgA nephropathy associated with MF,which developed into RPGN and subsequent end-stage renal disease.
Gupta, Ruchika; Sharma, Alok; Agarwal, Sanjay K; Dinda, Amit K
C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN) has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH). Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman's capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.
Reynolds, John; Abbott, Danielle S.; Karegli, Julieta; Evans, David J.; Pusey, Charles D.
Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the α 3 chain of type IV collagen, α3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat α3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 μg had no effect, a dose of 1000 μg resulted in a moderate reduction in EAG severity, and a dose of 3000 μg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of α3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture’s disease and other autoimmune disorders. PMID:19406992
Müller, G A; Gebhardt, M; Kömpf, J; Baldwin, W M; Ziegenhagen, D; Bohle, A
Frequencies of the HLA antigens ABC, DR and MT, as well as of the properdin factor alleles were determined in 24 unrelated patients presenting with immune complex mediated idiopathic rapidly progressive glomerulonephritis (RPGN) type II. As in Goodpasture syndrome (RPGN type I with pulmonary hemorrhage), a significant association with the B-cell alloantigen HLA-DR 2 was demonstrated (relative risk for HLA-DR 2 positive individuals was 3.54; P less than 0.01). In addition a marked increase of the HLA specificity MT 3 was shown, which is supposed to belong to an antigen system of a second HLA-D region locus. The highest relative risk of 14.67 (P less than 0.00001), however, was calculated for all patients carrying the BfF phenotype. Increased numbers of patients positive for HLA-DR 2 and -MT 3, as well as BfF suggested immune response genes or disease-related mutations on different haplotypes responsible for a MHC (major histocompatibility complex) associated predisposition of RPGN type II.
Guo, Qiao-Yan; Wu, Man; Wang, Yang-Wei; Sun, Guang-Dong
Hepatitis C virus (HCV) is a major cause of liver-associated morbidity and has an increasing prevalence worldwide. Hepatitis C virus infection may lead to chronic hepatitis, cirrhosis and liver failure. However, it is also associated with a wide range of extra-hepatic complications, such as cryoglobulinemia, an immune complex disease associated with cryoglobulin leading to multiple organ damage and, while the major symptom is vasculitis. The present study reported on a-58-year-old woman who was diagnosed with HCV-associated cryoglobulinemia with skin, kidney and blood system damage and biopsy-proven cryoglobulinemia membrano-proliferative glomerulonephritis. HCV RNA clearance occurred within a few weeks of interferon treatment and the patient was then treated by prednisolone and sustained interferon. While the therapeutic effect was obvious at first, the disease reappeared in combination with refractory infection and multiple organ failure, and the patient finally died. HCV-associated cryoglobulinemia is uncommon in developing countries such as China, while treatment guidelines remain to be established, particularly if complex complications are present.
Kang, Ju Hyung; Baik, Haing Woon; Yoo, Seung-Min; Kim, Joo Heon; Cheong, Hae Il; Park, Chung-Gyu; Kang, Hee Gyung; Ha, Il-Soo
Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns). We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). IgG deposition and expressions of FcRn and PRR were enhanced at glomeruli and urinary IgG levels increased in anti-GBM GN. Aliskiren attenuated anti-GBM GN with reduction of proteinuria and cortical expressions of fibronectin and TGF-β1. In addition, aliskiren suppressed the renal cortical expressions of FcRn and PRR. Aliskiren also reduced the glomerular IgG depositions and the urinary IgG levels albeit with increased circulating serum IgG levels. These results suggest that suppression of FcRn and PRR and regulation of IgG metabolism may be related to the attenuation of anti-GBM GN by aliskiren. © 2016 S. Karger AG, Basel.
Zhang, Qian; Luan, Hong; Wang, Le; He, Fan; Zhou, Huan; Xu, Xiaoli; Li, Xingai; Xu, Qing; Niki, Toshiro; Hirashima, Mitsuomi; Xu, Gang; Lv, Yongman; Yuan, Jin
Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.
Nabokov, A V; Travkina, E S; Zel'tser, G L; Nevorotin, A I
Kidney biopsy specimens obtained from a group of individuals with chronic glomerulonephritis (CGN) have been processed for light and electron microscopic immunolocalization of total immunoglobulins (Igs). In a few cases, acid phosphatase (ACPase), a lysosomal enzyme marker, was ultrastructurally visualized. In the glomeruli, horseradish peroxidase-stained Igs were revealed in capillary lumina, urinary spaces and in transit through occasional loci of the glomerular basal membranes while ACPase-containing lysosomes resided both within and outside the cells. In the proximal tubules, Igs were traced in the endocytic vesicles and vacuoles, the latter also being positive for ACPase. Statistically significant relationships have been revealed between the number of IGs-labeled proximal tubules and some clinical or pathomorphological stigmata of CGN, in particular, proteinuria and arterial hypertension levels, marked interstitial sclerosis, etc. The data obtained are discussed in regard to the mechanisms of increased macromolecular filtration and the different proteinuria selectivity levels as well as the development of interstitial sclerosis as a result of the elevated reabsorption and incomplete lysosomal degradation of Igs in CGN.
Guo, Qiao-Yan; Wu, Man; Wang, Yang-Wei; Sun, Guang-Dong
Hepatitis C virus (HCV) is a major cause of liver-associated morbidity and has an increasing prevalence worldwide. Hepatitis C virus infection may lead to chronic hepatitis, cirrhosis and liver failure. However, it is also associated with a wide range of extra-hepatic complications, such as cryoglobulinemia, an immune complex disease associated with cryoglobulin leading to multiple organ damage and, while the major symptom is vasculitis. The present study reported on a-58-year-old woman who was diagnosed with HCV-associated cryoglobulinemia with skin, kidney and blood system damage and biopsy-proven cryoglobulinemia membrano-proliferative glomerulonephritis. HCV RNA clearance occurred within a few weeks of interferon treatment and the patient was then treated by prednisolone and sustained interferon. While the therapeutic effect was obvious at first, the disease reappeared in combination with refractory infection and multiple organ failure, and the patient finally died. HCV-associated cryoglobulinemia is uncommon in developing countries such as China, while treatment guidelines remain to be established, particularly if complex complications are present. PMID:28810602
Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...
Butler, Louise; Brockley, Tomos; Denning, David; Richardson, Malcolm; Chisholm, Roger; Sinha, Smeeta; O’Driscoll, Ronan
A non-immunocompromised man developed acute Aspergillus pneumonia after spreading mouldy tree bark mulch. Despite normal renal function at presentation, he developed rapidly progressive glomerulonephritis with acute kidney injury due to anti-glomerular basement membrane antibodies (anti-GBM) 4 weeks later. He remained dialysis dependent and died of sepsis 10 months later. We hypothesise that he contracted invasive pulmonary Aspergillosis from heavy exposure to fungal spores, leading to epitope exposure in the alveoli with subsequent development of GBM auto-antibodies. PMID:24432235
Butler, Louise; Brockley, Tomos; Denning, David; Richardson, Malcolm; Chisholm, Roger; Sinha, Smeeta; O'Driscoll, Ronan
A non-immunocompromised man developed acute Aspergillus pneumonia after spreading mouldy tree bark mulch. Despite normal renal function at presentation, he developed rapidly progressive glomerulonephritis with acute kidney injury due to anti-glomerular basement membrane antibodies (anti-GBM) 4 weeks later. He remained dialysis dependent and died of sepsis 10 months later. We hypothesise that he contracted invasive pulmonary Aspergillosis from heavy exposure to fungal spores, leading to epitope exposure in the alveoli with subsequent development of GBM auto-antibodies.
Upadhaya, Bala Krishna; Sharma, Alok; Khaira, Ambar; Dinda, Amit K; Agarwal, Sanjay K; Tiwari, Suresh C
Dengue virus infection can clinically manifest as dengue fever, dengue shock syndrome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15-year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.
Ramírez Ponferrada, R; Gallardo Avilla, A; Solís García, E; Castilla, J M; Martínez, R; Rodríguez, B
A relation between kidney and inner ear disease, specifically neurosensorial hearing loss, has been established. Likewise, the role of tonsillitis in certain glomerulonephritides is well known. A case of post-streptococcal mesangial glomerulonephritis with IgA deposit (Berger's disease) and neurosensorial hearing loss is reported. The absence of any relevant family or personal history suggests an immunological origin for both disorders.
Scandiuzzi, Lisa; Beghdadi, Walid; Daugas, Eric; Åbrink, Magnus; Tiwari, Neeraj; Brochetta, Cristiana; Claver, Julien; Arouche, Nassim; Zang, Xingxing; Pretolani, Marina; Monteiro, Renato C.; Pejler, Gunnar; Blank, Ulrich
Mast cells exert protective effects in experimental antiglomerular basement membrane-induced glomerulonephritis (GN), yet the responsible mediators have not been identified. In this study, we investigated the role of mouse mast cell protease (mMCP)-4, the functional homolog of human chymase, using mMCP-4–deficient mice. Compared with wild type animals, mMCP-4–deficient mice exhibited lower proteinuria, blood creatinine, and blood urea nitrogen levels, indicating an aggravating role of mMCP-4. Kidney histology confirmed less severe renal damage in mMCP-4–deficient mice with reduced deposits, glomerular and interstitial cellularity, and fibrosis scores. High amounts of mMCP-4 were detected in renal capsules, but not in the whole kidney, from wild type mice. Its expression in renal capsules was markedly decreased after GN induction, suggesting that locally released enzyme by degranulated mast cells could contribute to the functional and physiopathological hallmarks of GN. Supporting a proinflammatory role, glomerular and interstitial macrophage and T cell infiltration, levels of proinflammatory TNF and MCP-1 mRNA, and the expression of the profibrotic peptide angiotensin II together with type I collagen were markedly down-regulated in kidneys of mMCP-4–deficient mice. We conclude that mMCP-4 chymase, contrary to the global anti-inflammatory action of mast cells, aggravates GN by promoting kidney inflammation. These results highlight the complexity of mast cell-mediated inflammatory actions and suggest that chymase inhibition may represent a novel therapeutic target in GN. PMID:20530261
Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie
Abstract The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID:27258503
Rollino, Cristiana; Coppo, Rosanna; Giacchino, Franca; Savoldi, Silvana; Manganaro, Marco; Amore, Alessandro; Colla, Loredana; Ferro, Michela; Demicheli, Giovanni; Berutti, Silvia; Burdese, Manuel; Paternoster, Giuseppe; Cravero, Raffaella; Benozzi, Luisa; Vagelli, Giuseppe; Messuerotti, Alessandra; Licata, Carolina; Bainotti, Serena; Patti, Rosaria Rita; Quaglia, Marco; Costantini, Luigia; Stratta, Piero; Segoloni, Giuseppe
The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.
Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie
The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome.A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome.The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%).In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options.
Tani, C; Mosca, M; d'Ascanio, A; Neri, R; Tavoni, A; Carli, L; Bombardieri, S
To evaluate the long- term outcome of a group of systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide (Cyc) in order to find out baseline predictor variables of disease outcome at the end of the follow-up. Female SLE patients fulfilling ACR criteria with active DPGN treated with pulse steroids and pulse Cyc were enrolled in the study and retrospectively analyzed with particular interest to renal flares and poor renal outcome at the end of follow- up as outcome measures. 30 female patients with DPGN were included, of these 20 (66,7%) patients are actually in follow-up at our unit, 4 (13.3%) died and 6 (20%) were lost during the follow-up. Fourteen patients (46.6%) presented at least one renal flare (RF) during the follow up for a total of 21 flares. At our last observation, 18 (60%) presented a good renal outcome while 12 (40%) had a poor outcome. Lower age at kidney biopsy resulted an important prognostic factor for the occurrence of both RF and poor long- term renal outcome; additionally, a poor renal outcome resulted significantly correlated with an inadequate response at the end of the protocol and with the number of renal flares after remission. These data suggest that, in general, a short course therapy with Cyc might be effective in controlling disease activity but demonstrated high rate of RF and poor renal outcome over time; however, this protocol might represent an effective therapeutic strategy in a subgroup of patients with specific epidemiological and clinical characteristics and suggest the possibility of tailoring immunosuppressive therapy on the basis of prognostic factor at baseline.
Sumida, Keiichi; Ubara, Yoshifumi; Marui, Yuji; Nakamura, Michio; Takaichi, Kenmei; Tomikawa, Shinji; Fujii, Takeshi; Ohashi, Kenichi
Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a recently described disease entity. In the kidney transplantation literature, only 6 recurrent and 2 de novo PGNMID cases, including 7 of the IgG3 subclass (6 with κ light chain and 1 with λ light chain) and 1 of the IgG1 subclass (λ light chain), have been described to date. We describe a 52-year-old man with end-stage renal disease whose primary glomerular disease had been suggested to be membranoproliferative glomerulonephritis. The patient underwent living related donor kidney transplantation and presented with proteinuria, hematuria, and decreased kidney function at 4 months posttransplantation. Biopsy of the transplanted kidney showed diffuse endocapillary proliferative glomerulonephritis. Immunofluorescence microscopy showed prominent granular glomerular staining for IgG, C3, and λ light chain, with IgM, IgA, and κ light chain undetectable. Immunofluorescence staining for IgG subclass showed signal for IgG2 only. Retrospective analysis of the native kidney biopsy specimen also showed the same monoclonal glomerular staining for the IgG2λ subtype. These findings led us to the diagnosis of PGNMID of the IgG2λ subtype as both the primary glomerular disease and recurrent disease in the transplanted kidney. Recurrence was treated with high-dose prednisolone, which decreased proteinuria, hematuria, and serum creatinine level. The case demonstrates that PGNMID of the IgG2λ subtype also can recur in the transplanted kidney.
Song, Jingjing; Wang, Yingwu; Liu, Chungang; Huang, Yan; He, Liying; Cai, Xueying; Lu, Jiahui; Liu, Yan; Wang, Di
Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent.
Background Renal biopsies provide important diagnostic and prognostic information in ANCA associated glomerulonephritis. A new classification for prognostication of pauci-immune glomerulonephritis (GN) based on four categories (Mixed, Crescentic, Sclerotic and Focal) was proposed by an international working group of renal pathologists (IWGRP). The goal of our study was to apply the proposed classification system to a United States cohort of vasculitis patients and determine the association of IWGRP class with estimated glomerular filtration rate (eGFR) at one year. Methods Seventy-six cases of pauci-immune glomerulonephritis diagnosed from 1995 to 2011 from a single center were identified for this retrospective study. Clinical data were collected by abstraction from medical records. Histology was reviewed by a pathologist and classified according to the new classification. MDRD formula was used to calculate eGFR. We correlated IWGRP class to renal function at presentation and at one year. ×2, ANOVA, and linear regression analysis were performed as appropriate. Results Renal biopsies were categorized as focal: n = 20, crescentic: n = 18, mixed: n = 27, sclerotic: n = 11. The baseline e-GFR was lowest in the crescentic class and highest in the focal class. In linear regression analysis investigating e-GFR at 1 year; age and baseline e-GFR were independent predictors of e-GFR at 1 year. Conclusions The e-GFR at diagnosis and age were predictors of e-GFR at 1 year. Pathologic class at diagnosis may also be a helpful tool in risk stratification at diagnosis. PMID:24093336
Chen, Yung-Ming; Chiang, Wen-Chih; Yang, Yalin; Lai, Chun-Fu; Wu, Kwan-Dun; Lin, Shuei-Liong
Anti-Thy1 glomerulonephritis is a rat nephritis model closely simulating human mesangial proliferative glomerulonephritis. It affects primarily the mesangium, yet displays substantial proteinuria during the course. This study investigated the molecular signals underlying proteinuria in this disease and the modulation of which by the known antiproteinuric agent, pentoxifylline. Male Wistar rats were randomly divided into a control group and nephritic groups with or without treatment with IMD-0354 (an IκB kinase inhibitor), SB431542 (an activin receptor–like kinase inhibitor) or pentoxifylline. Kidney sections were prepared for histological examinations. Glomeruli were isolated for mRNA and protein analysis. Urine samples were collected for protein and nephrin quantitation. One day after nephritis induction, proteinuria developed together with ultrastructural changes of the podocyte and downregulation of podocyte mRNA and protein expression. These were associated with upregulation of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β/activins mRNAs and activation of nuclear factor (NF)-κB p65 and Smad2/3. IMD-0354 attenuated proteinuria on d 1, whereas SB431542 decreased proteinuria on d 3 and 5, in association with partial restoration of downregulated podocyte mRNA and protein expression. Pentoxifylline attenuated proteinuria and nephrinuria through the course, plus inhibition of p-NF-κB p65 (d 1) and p-Smad2/3 (d 5) and partial reversal of downregulated podocyte mRNA and protein. Our data show that the pathogenesis of proteinuria in anti-Thy1 glomerulonephritis involves TNF-α and TGF-β/activin pathways, and the evolution of this process can be attenuated by pentoxifylline via downregulation of NF-κB and Smad signals and restoration of the podocyte component of the glomerular filtration barrier. PMID:25879629
Okuda, S; Languino, L R; Ruoslahti, E; Border, W A
Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological
Kato, Akihiko; Sugiura, Takeshi; Yamamoto, Tatsuo; Misaki, Taro; Tsuji, Takayuki; Sakao, Yukitoshi; Sakakima, Masaaki; Yasuda, Hideo; Fujigaki, Yoshihide; Hishida, Akira
We reported the case of a 70-year-old woman with moderate renal failure due to anti-neutrophil cytoplasmic antibody-related glomerulonephritis who developed symptomatic water intoxication (serum Na: 108 mEq/L) following treatment with oral low-dose cyclophosphamide (CY) (50mg/day). Estimated glomerular filtration rate was 29.5 mL/min/1.73 m(2). She had drunk >2 L of fluid in 12 h prior to the development of cerebral oedema. This rare case suggests that oral low-dose CY could be an occult cause of water intoxication in patients with chronic kidney disease taking large fluid volumes.
Kamezaki, Michitsugu; Kusaba, Tetsuro; Adachi, Takaomi; Yamashita, Noriyuki; Nakata, Mayumi; Ota, Noriyoshi; Shiotsu, Yayoi; Ishida, Mami; Usui, Takeshi; Tamagaki, Keiichi
Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disease caused by GATA3 mutations. Although several cases with variable renal features have been reported, the presence of histological changes within the glomeruli in adult patients is unclear. We herein report an adult case of HDR syndrome with a novel p.C288W (TGC>TGG) missense mutation in GATA3. His renal histology showed a membranoproliferative glomerulonephritis-like glomerular lesion. Additional renal histological analyses of HDR syndrome patients will be needed to clarify the role of GATA3 in both the developing and adult kidney.
Mandal, A K; Baig, M; Koutoubi, Z
urine output and urinary sodium excretion, and a rapid decrease in blood urea nitrogen, constitutes strong evidence for prerenal ARF. However, these indices are unreliable when prerenal ARF has progressed to ATN or when ARF has an obstructive pattern to begin with. In all cases of ARF, especially in elderly men, urinary tract obstruction should be suspected unless the history is otherwise clear cut. Ultrasound of the kidneys and bladder is a simple, non-invasive and meaningful test that can be used to rule out obstructive causes of ARF. If obstruction is the cause of ARF, ultrasound will be positive; in contrast, urinary obstruction is very unlikely if ultrasound findings are normal in a patient who has been oliguric or anuric for 48 hours or more. Similarly, acute glomerulonephritis, including rapidly progressive glomerulonephritis, should be suspected when ARF is associated with heavy proteinuria. In such instances, percutaneous renal biopsy is essential to document the diagnosis. It is of utmost importance to establish whether ARF is of prerenal or postrenal type, both of which are potentially fully reversible. In contrast, patients with ATN or rapidly progressive glomerulonephritis may not recover, or may only partially recover, their renal function. Haemodialysis and nutritional support are common measures for patients with severe ATN and a highly catabolic state. Corticosteroids and immunosuppressive therapy should be instituted for rapidly progressive glomerulonephritis, in addition to haemodialysis. haemodiafiltration instead of haemodialysis is recommended for patients who are haemodynamically unstable [i.e., with a persistently low blood pressure (systolic < or = 100 mm Hg)]. Haemodiafiltration has been shown to improve acid-base balance and uraemia better than standard haemodialysis. However, despite dialysis, mortality in patients with ARF associated with ischaemic ATN remains high.
Wu, Chien-Te; Fu, Lin-Shien; Wen, Mei-Chin; Hung, Shein-Chung; Chi, Ching-Shiang
Several risk factors have been associated with the prognosis of lupus nephritis. However, few studies have focused on renal vascular lesions (such as thrombi due to immune complexes) as a prognostic factor in this disease. Here we present a case of systemic lupus erythematosus (SLE) in a 12-year-old girl who exhibited acute renal failure and severe hypertension on admission. Renal pathology findings included diffuse proliferative glomerulonephritis (class IVb) and lupus vasculopathy (LV) with immune complex deposition within glomerular capillaries and the preglomerular arteriolar lumen. Her clinical condition deteriorated rapidly, even after cyclophosphamide and methylprednisolone pulse therapy. It improved after 5 days of plasmapheresis and remained stable for up to 6 months under regular treatment. We suggest that renal biopsy performed early in SLE patients with renal involvement should be studied carefully for the presence of vascular lesions. Additionally, plasmapheresis can be considered in patients with LV refractory to other modalities of therapy.
Rasla, Somwail; El Meligy, Amr; Cucu, Dragos F
We report a rare case of Hydralazine-induced ANCA associated glomerulonephritis with alveolar hemorrhage in the setting of acute Clostridium Difficile Infection. A 71-year-old Caucasian woman with hypertension, who was being treated with hydralazine 25 mg twice a day for six years, presented to the hospital with diarrhea, nausea, vomiting and anemia. She had acute kidney injury and urinalysis showed proteinuria, dysmorphic RBCs, and rare RBC cast. She was found to have Clostridium difficile colitis which was successfully treated. She became hypoxemic; CT scan findings showed bilateral pulmonary infiltrates. Broncho-alveolar lavage was consistent with pulmonary hemorrhage. Kidney biopsy revealed focal segmental necrotizing and diffuse crescentic glomerulonephritis, pauci-immune type (ANCA-associated). Hydralazine was discontinued and the patient was treated with corticosteroids, intravenous cyclophosphamide and plasmapheresis. To our knowledge, hydralazine-associated low complement in the setting of C-diff infection has not been previously reported. This is considered a potentially life-threatening condition requiring immediate discontinuation of the offending medication and expedited lifesaving measures. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].
Sun, Jian-Yong; Sun, Yu; Wu, Hui-Juan; Zhang, Hong-Xia; Zhao, Zhong-Hua; Chen, Qi; Zhang, Zhi-Gang
Polyethylenimine (PEI), a cationic polymer, is one of the most efficient non-viral vectors for transgene therapy. Decorin (DCN), a leucine-rich proteoglycan secreted by glomerular mesangial cells (MC), is a promising anti-fibrotic agent for the treatment of glomerulonephritis. In this study, we used PEI-DCN nanocomplexes with different N/P ratios to transfect MC in vitro and deliver the MC vector with PEI-DCN expressing into rat anti-Thy1.1 nephritis kidney tissue via injection into the left renal artery in vivo. The PEI-plasmid DNA complex at N/P 20 had the highest level of transfection efficiency and the lowest level of cytotoxicity in cultured MC. Following injection, the ex vivo gene was transferred successfully into the glomeruli of the rat anti-Thy1.1 nephritis model by the MC vector with the PEI-DCN complex. The exogenous MC with DCN expression was located mainly in the mesangium and the glomerular capillary. Over-expression of DCN in diseased glomeruli could result in the inhibition of collagen IV deposition and MC proliferation. The pathological changes of rat nephritis were alleviated following injection of the vector. These findings demonstrate that the DCN gene delivered by the PEI-DNA nanocomplex with the MC vector is a promising therapeutic method for the treatment of glomerulonephritis.
Mou, Shan; Li, Jialin; Yu, Zanzhe; Wang, Qin; Ni, Zhaohui
An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.
Toda, Naohiro; Mori, Kiyoshi; Kasahara, Masato; Ishii, Akira; Koga, Kenichi; Ohno, Shoko; Mori, Keita P.; Kato, Yukiko; Osaki, Keisuke; Kuwabara, Takashige; Kojima, Katsutoshi; Taura, Daisuke; Sone, Masakatsu; Matsusaka, Taiji; Nakao, Kazuwa; Mukoyama, Masashi; Yanagita, Motoko; Yokoi, Hideki
Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction. Although CTGF is expressed by podocytes at basal levels, podocyte-specific CTGF (pod-CTGF) cKO mice showed no improvement in renal injury. In contrast, PDGFRα promoter-driven CTGF (Pdgfra-CTGF) cKO mice, which predominantly lack CTGF expression by mesangial cells, exhibited reduced proteinuria with ameliorated histological changes. Glomerular macrophage accumulation, expression of Adgre1 and Ccl2, and ratio of M1/M2 macrophages were all reduced both in Rosa-CTGF cKO and Pdgfra-CTGF cKO mice, but not in pod-CTGF cKO mice. TGF-β1-stimulated Ccl2 upregulation in mesangial cells and macrophage adhesion to activated mesangial cells were decreased by reduction of CTGF. These results reveal a novel mechanism of macrophage migration into glomeruli with nephritis mediated by CTGF derived from mesangial cells, implicating the therapeutic potential of CTGF inhibition in glomerulonephritis. PMID:28191821
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... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...
Pulin, A A; Brovko, M Iu; Kustova, T Iu; Kozlovskaia, L V; Fomin, V V; Mukhin, N A
To determine the nature and magnitude of changes in the detectable serum and urinary biomarkers of water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis (CGN), their importance for assessing the activity and prognosis of the disease. Forty-seven patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased renal function; Group 2 comprised 16 patients with persistent NS and normal renal function; Group 3 consisted of 10 patients with partial remission of NS; Group 4 included 11 patients with active hematuric CGN. A control group consisted of 9 healthy individuals matched for gender and age with the patients with CGN. The serum level of copeptin and the urinary excretion of aquaporine-2 (AQP-2) and kidney injury molecule-1 (KIM-1) were determined by indirect enzyme-linked immunosorbent assay (ELISA). In the NS patients with and without renal dysfunction, the serum copeptin concentration was significantly higher than that in those with partial remission of NS or hematuric CGN and in the controls. In the patients with hematuric CGN, this indicator was virtually different from that in the control group. Urinary AQP-2 excretion was significantly similar in 3 NS groups. In the patients with hematuric CGN, the urinary AQP-2 concentration was higher than that in those with NS, but it was significantly lower than in the control group. The highest urinary excretion of KIM-1 was found in the patients with NS and diminished renal function while its excretion was significantly lower in the patients with NS and stable renal function, as in those with partial remission of NS. The lowest values were seen in the patients with hematuric CGN and in the control group; the differences between these groups were statistically insignificant. Correlation analysis showed that there was an inverse correlation between serum copeptin and urinary AQP-2 levels and between urinary AQP- 2 and KIM-1 levels. Serum copeptin
Haider, Dominik G; Masghati, Salome; Goliasch, Georg; Fuhrmann, Valentin; Soleiman, Afschin; Wolzt, Michael; Baierl, Andreas; Druml, Wilfred; Hörl, Walter H
Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN). In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Full data sets were available from 1,892 subjects. Classes of CKD on the basis of estimated GFR (eGFR) and of proteinuria grouped as <1, 1-3.5, and >3.5 g/24 h were tested for their association with all-cause mortality and ESRD. During a median follow-up of 130 months [interquartile range (IQR) 90; 178] 478 patients (25.3 %) died. Median eGFR was 49 ml/min/1.73 m(2) (IQR 24; 81) and proteinuria 3.8 g/24 h (IQR 1.7; 8.0). Adjusted multivariate Cox regression indicated that renal survival but not overall survival is related to proteinuria >3.5 g/24 h [as opposed to <1 g/24 h; hazard ratio (HR) 1.91] and shows progression to ESRD. However, subgroup analyses revealed that this risk with proteinuria >3.5 g/24 h exists only in patients with immunoglobulin (Ig)A GN (HR 4.93), miscellaneous GN (HR 1.74), and CKD stage 5 (HR 2.50). Additionally, proteinuria is a risk factor for renal survival in males more than in females with GN and proteinuria >3.5 g/24 h (HR 1.91). Proteinuria is a strong risk factor for renal survival particularly in patients with proteinuria >3.5 g/24 but not for all types of GN, nor for all CKD stages. Proteinuria is not a risk factor for overall survival in patients with GN.
Besur, Siddesh; Schmeltzer, Paul; Bonkovsky, Herbert L
Porphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP). AIP is the most common, and ALADP is the least common acute porphyria. The clinical presentations of acute porphyrias are nonspecific. There are no pathognomonic signs or symptoms. The most frequent presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. Hyponatremia is the most common electrolyte abnormality during acute attacks, and hypomagnesemia is also common. Both are risk factors for development of seizures, which occur in ∼ 20-30% of acute attacks. Once suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality. Acute attacks last a few days, and the majority of patients are asymptomatic between attacks. Prognosis is good if the condition is recognized early and treated aggressively. Copyright © 2015 Elsevier Inc. All rights reserved.
... Chronic Kidney Disease Kidneys and Urinary Tract Kidney Stones Ultrasound: Renal (Kidneys, Ureters, Bladder) When Your Child ... Blood in the Urine (Hematuria) Kidney Disease Kidney Stones Kidney Transplant Kidneys and Urinary Tract Dialysis Lupus ...
Singri, Naveen; Gleason, Briana; Flamm, Steve L; Kanwar, Yashpal S; Ghossein, Cybele
Patients with end-stage liver disease are prone to hemodynamic and immunologic renal injury, the latter at times manifesting as glomerulonephritis. Elevated serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in these patients, but are often clinically silent. We report a patient with autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli having undergone crescentic change, and with IgA2 deposits in the glomerular mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic management.
Kato, Akihiko; Sugiura, Takeshi; Yamamoto, Tatsuo; Misaki, Taro; Tsuji, Takayuki; Sakao, Yukitoshi; Sakakima, Masaaki; Yasuda, Hideo; Fujigaki, Yoshihide; Hishida, Akira
We reported the case of a 70-year-old woman with moderate renal failure due to anti-neutrophil cytoplasmic antibody-related glomerulonephritis who developed symptomatic water intoxication (serum Na: 108 mEq/L) following treatment with oral low-dose cyclophosphamide (CY) (50mg/day). Estimated glomerular filtration rate was 29.5 mL/min/1.73 m2. She had drunk >2 L of fluid in 12 h prior to the development of cerebral oedema. This rare case suggests that oral low-dose CY could be an occult cause of water intoxication in patients with chronic kidney disease taking large fluid volumes. PMID:18795141
Sawanobori, E; Umino, A; Kanai, H; Matsushita, K; Iwasa, S; Kitamura, H; Oda, T; Yoshizawa, N; Sugita, K; Higashida, K
We herein report the case of a 12-year-old boy with dense deposit disease (DDD) evoked by streptococcal infection. He had been diagnosed to have asymptomatic hematuria syndrome at the age of 6 during school screening. At 12 years of age, he was found to have macrohematuria and overt proteinuria with hypocomplementemia 2 months after streptococcal pharyngitis. Renal biopsy showed endocapillary proliferative glomerulonephritis with double contours of the glomerular basement membrane. Hypocomplementemia and proteinuria were sustained for over 8 weeks. He was suspected to have dense deposit disease due to intramembranous deposits in the first and the second biopsies. 1 month after treatment with methylprednisolone pulse therapy, proteinuria decreased to a normal level. Microscopic hematuria disappeared 2 years later, but mild hypocomplementemia persisted for more than 7 years. Nephritis-associated plasmin receptor (NAPlr), a nephritic antigen for acute poststreptococcal glomerulonephritis, was found to be positive in the glomeruli for more than 8 weeks. DDD is suggested to be caused by dysgeneration of the alternative pathway due to C3NeF and impaired Factor H activity. A persistent deposition of NAPlr might be one of the factors which lead to complement dysgeneration. A close relationship was suggested to exist between the streptococcal infection and dense deposit disease in this case.
Thongboonkerd, Visith; Luengpailin, Jirapon; Cao, Junkai; Pierce, William M; Cai, Jian; Klein, Jon B; Doyle, R J
Fluoridation causes an obvious reduction of dental caries by interference with cariogenic streptococci. However, the effect of fluoride on group A streptococci that causes rheumatic fever and acute poststreptococcal glomerulonephritis is not known. We have used proteomic analysis to create a reference proteome map for Streptococcus pyogenes and to determine fluoride-induced protein changes in the streptococci. Cellular and extracellular proteins were resolved by two-dimensional polyacrylamide gel electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry. 183 protein spots were visualized, and 74 spots representing 60 unique proteins were identified. A 16-h exposure to sodium fluoride caused decreased expression of proteins required to respond to cellular stress, including anti-oxidants, glycolytic enzymes, transcriptional and translational regulators, and protein folding. Fluoride caused decreased cellular expression of two well-characterized S. pyogenes virulence factors. Fluoride decreased expression of glyceraldehyde-3-phosphate dehydrogenase, which acts to bind fibronectin and promote bacterial adherence. We also performed proteomic analysis of protein released by S. pyogenes into the culture supernatant and observed decreased expression of M proteins following fluoride exposure. These data provide evidence that fluoride causes decreased expression by S. pyogenes proteins used to respond to stress, virulence factors, and implicated in non-suppurative complications of S. pyogenes, including glomerulonephritis and rheumatic fever.
Subramaniam, S. Ravih; Cader, Rizna Abdul; Mohd, Rozita; Yen, Kong Wei; Ghafor, Halim Abdul
Patient: Male, 48 Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of cyclophosphamide Clinical Procedure: — Specialty: Nephrology • Hepatology • Gastroenterology • Toxicology Objective: Unexpected drug reaction Background: Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow suppression, hemorrhagic cystitis, nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide is well recognized but hepatitis due to low dose cyclophosphamide has rarely been described. Case Report: We report the case of a 48-year-old Chinese man with a rapidly progressive glomerulonephritis secondary to granulomatosis with polyangiitis who developed severe acute hepatic failure within 24 hours of receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis with polyangiitis was supported with a positive c-ANCA serology. The patient was treated with high dose methylprednisolone, plasmapheresis, intermittent hemodialysis, and low-dose intravenous cyclophosphamide. Conclusions: Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide treatment. To the best of our knowledge, this is the first report of severe, non-viral, liver inflammation developing within 24 hours of administration of low-dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this serious adverse reaction and should not repeat the cyclophosphamide dose when there is hepatotoxicity caused by the first dose. Initial and follow-up liver function tests should be monitored in all patients receiving cyclophosphamide treatment. PMID:24023976
Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg; Kumagai, Kazuyoshi; Harkema, Jack R.; Holian, Andrij; Pestka, James J.
Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis. PMID:25978333
Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi
The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
Val-Bernal, J F; Garijo, M F; Val, D; Rodrigo, E; Arias, M
Although the diagnosis of membranous glomerulonephritis (MGN) may be suspected on routine histology of formalin-fixed paraffin-embedded tissue, fresh-frozen tissue must be used to show the immunologic nature of the process by direct immunofluorescence (IF). The efficiency of IF or immunoperoxidase (IP) detection of IgG and C3 using paraffin sections is controversial. This study was designed to evaluate whether glomerular C4d deposition using an IP method in formalin-fixed paraffin-embedded tissue may be a useful marker for MGN. We showed characteristic glomerular, granular basement membrane deposition of C4d in 31 (100%) cases of idiopathic MGN and in 5 cases (100%) of pure class V membranous lupus nephritis, in which we had a positive diagnosis of the lesions for conventional IF study. Control cases were negative. Nineteen cases of different glomerulopathies, including IgA nephropathy, primary type I membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis and minimal change disease showed diverse reproducible patterns of C4d deposition, without intrinsic background. Our results indicate that staining of formalin-fixed paraffin-embedded tissue for C4d can be used for confirmation of granular basement membrane immunoreactant deposition in cases of MGN. This proved to be a reliable method that could potentially obviate the need for rebiopsy in cases with absence of glomeruli in renal frozen sections or when other adjunct IF or IP methods on paraffin sections are negative. C4d immunostaining, using an IP method, deserves a place as an adjunct method in the biopsy diagnosis of MGN.
Dassan, Pooja; Clarke, Charles; Sharp, David J
High antistreptococcal antibody titer (ASOT) was measured in a 31-year-old Caucasian lady presenting with opsoclonus and myoclonus. She was treated with oral steroids and 8 weeks after the onset of symptoms she had a normal ASOT and only mild residual symptoms. This is one of the first cases of opsoclonus-myoclonus syndrome developing, following a streptococcal infection in adults.
... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...
... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...
... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...
Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A
Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.
... urine from your bladder and out through the penis Acute prostatitis may also be caused by problems ... urine out of the bladder Foreskin of the penis that cannot be pulled back (phimosis) Injury to ...
Activation of Autophagy and Nucleotide-Binding Domain Leucine-Rich Repeat–Containing-Like Receptor Family, Pyrin Domain–Containing 3 Inflammasome during Leishmania infantum–Associated Glomerulonephritis
Esch, Kevin J.; Schaut, Robert G.; Lamb, Ian M.; Clay, Gwendolyn; Morais Lima, Ádila L.; do Nascimento, Paulo R.P.; Whitley, Elizabeth M.; Jeronimo, Selma M.B.; Sutterwala, Fayyaz S.; Haynes, Joseph S.; Petersen, Christine A.
Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum–infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions. An ultrastructural evaluation of glomeruli from animals with VL identified mesangial cell proliferation and interposition. Immunohistochemistry demonstrated significant Leishmania antigen, IgG, and C3b deposition in VL dog glomeruli. Asymptomatic and symptomatic dogs had increased glomerular nucleotide-binding domain leucine-rich repeat–containing-like receptor family, pyrin domain containing 3 and autophagosome-associated microtubule-associated protein 1 light chain 3 associated with glomerular lesion severity. Transcriptional analyses from symptomatic dogs confirmed induction of autophagy and inflammasome genes within glomeruli and tubules. On the basis of temporal VL staging, glomerulonephritis was initiated by IgG and complement deposition. This deposition preceded presence of nucleotide-binding domain leucine-rich repeat–containing-like receptor family, pyrin domain containing 3–associated inflammasomes and increased light chain 3 puncta indicative of autophagosomes in glomeruli from dogs with clinical VL and renal failure. These findings indicate potential roles for inflammasome complexes in glomerular damage during VL and autophagy in ensuing cellular responses. PMID:26079813
Kalavrizioti, Dimitra; Gerolymos, Miltiadis; Rodi, Maria; Kalliakmani, Pantelitsa; Provatopoulou, Simela; Eleftheriadis, Theodoros; Mouzaki, Athanasia; Goumenos, Dimitrios S
Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function. Ninety-seven patients (62 M/35 F, age 53.1 ± 15.6 years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n=36), IgA nephropathy (IgAN, n=31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n=30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria. GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years. Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary
Kim, Eun Jung; Shin, Dong Ho; Jeon, Hee Jung; Rhee, So Yon; Nam, Eun Sook; Park, Ji Young
POEMS syndrome is a rare paraneoplastic syndrome and there are few reports of polyneuropathy and monoclonal gammopathy associated with kidney dysfunction. Here, we report a case of POEMS syndrome with recurrent acute kidney injury (AKI). A 52-year-old man presented with bilateral aggravating paresthesia and latermotor weakness of the lower extremities accompanied by repeated elevation of serum creatinine. The patient was finally diagnosed with POEMS syndrome on the basis of fulfilling the two mandatory major criteria (polyneuropathy and monoclonal gammopathy), one other major criterion (sclerotic bone lesion), and several minor criteria. A renal biopsy was performed to clarify the cause of AKI and showed membranoproliferative glomerulonephritis-like lesions with mesangiolysis and endothelial cell injury. This case illustrates that renal manifestations, not included in the diagnostic criteria for POEMS, can be apparent before various other systemic symptoms. PMID:27453713
Pepper, Ruth J; Hamour, Sally; Chavele, Konstantia-Maria; Todd, Sarah K; Rasmussen, Niels; Flint, Shaun; Lyons, Paul A; Smith, Kenneth G C; Pusey, Charles D; Cook, H Terence; Salama, Alan D
Antineutrophil cytoplasm antibody (ANCA)–associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochemistry of renal biopsies, patients with focal or crescentic glomerular lesions were found to have the highest expression of calprotectin and those with sclerotic the least. Serum levels of calprotectin as measured by ELISA were elevated in patients with active AAV and the levels decreased but did not normalize during remission, suggesting subclinical inflammation. Calprotectin levels in patients with limited systemic disease increased following treatment withdrawal and were significantly elevated in patients who relapsed compared with those who did not. As assessed by flow cytometry, patients with AAV had higher monocyte and neutrophil cell surface calprotectin expression than healthy controls, but this was not associated with augmented mRNA expression in CD14+ monocytes or CD16+ neutrophils. Thus, serum calprotectin is a potential disease biomarker in patients with AAV, and may have a role in disease pathogenesis. PMID:23423260
[Extramembranous glomerulonephritis of acquired syphilis in a patient recently infected by the hepatitis B virus. Demonstration of the treponemal antigen in the kidney by indirect immunofluorescence].
Schillinger, F; Montagnac, R; Goclowski, C; Dine, G; Alessandri, E; Hopfner, C; Birembaut, P
A 38 years old male homosexual with active secondary syphilis presented with pure nephrotic syndrome while HBs and HBe tests were positive without clinical hepatitis. He had circulating immune complexes, IgG--IgM cryoglobulinemia and high IgA, IgM and IgE levels; the C3 and C4 complement constituents were normal. Examination of renal biopsy sections under light, fluorescent and electronic microscopy showed stage I membranous glomerulonephritis the syphilitic origin of which was confirmed by indirect immunofluorescence and by rapid cure under penicillin treatment. This case calls for the following comments: (1) glomerular deposits are extramembranous rather than subendothelial in syphilitic nephrosis, a disease now classified among circulating immune complexes diseases; (2) in the kidney, the treponema antigen can be demonstrated by indirect immunofluorescence and the anti-treponema antibody, by elution; (3) the outcome of the nephrotic syndrome is always favourable, either spontaneously or after penicillin treatment; (4) syphilis and HBs antigens are frequently associated, particularly in homosexual patients; one should be looked for when the other is discovered.
Sartori, A; Roque-Barreira, M C; Coe, J; Campos-Neto, A
In a previous report analysing kidney sections by immunofluorescence we showed that hamsters infected with L. donovani develop a glomerulonephritis (GN) associated with deposition of hamster immunoglobulins and parasite antigens in the glomeruli. In this study we characterize these immune components eluted from the kidneys. The eluted immunoglobulins showed specificity for L. donovani antigens and hamster immunoglobulins (rheumatoid factor-like activity). The four isotypes IgG1, IgG2, IgA and IgM were detected. Several L. donovani antigens were detected in the renal eluates by Western blot and immunoprecipitation using 125I-labelled eluates. Proteins with mol. wt of 134, 82, 52, 31, and 26 kD were detected by Western blot and proteins with 134, 110, 93, 89 and 48 kD were detected by immunoprecipitation. With the exception of the 134 kD protein which was recognized by both rabbit anti-promastigote and rabbit anti-amastigote sera all the others were recognized only by the anti-amastigote serum. The 134 kD protein was the only one isolated from the kidneys of infected hamster immunocomplexed with IgG and was the only one detected in a promastigote lysate using IgG from L. donovani-infected hamsters. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1544224
Kinkade, Scott; Long, Natalie A
Cough is the most common illness-related reason for ambulatory care visits in the United States. Acute bronchitis is a clinical diagnosis characterized by cough due to acute inflammation of the trachea and large airways without evidence of pneumonia. Pneumonia should be suspected in patients with tachypnea, tachycardia, dyspnea, or lung findings suggestive of pneumonia, and radiography is warranted. Pertussis should be suspected in patients with cough persisting for more than two weeks that is accompanied by symptoms such as paroxysmal cough, whooping cough, and post-tussive emesis, or recent pertussis exposure. The cough associated with acute bronchitis typically lasts about two to three weeks, and this should be emphasized with patients. Acute bronchitis is usually caused by viruses, and antibiotics are not indicated in patients without chronic lung disease. Antibiotics have been shown to provide only minimal benefit, reducing the cough or illness by about half a day, and have adverse effects, including allergic reactions, nausea and vomiting, and Clostridium difficile infection. Evaluation and treatment of bronchitis include ruling out secondary causes for cough, such as pneumonia; educating patients about the natural course of the disease; and recommending symptomatic treatment and avoidance of unnecessary antibiotic use. Strategies to reduce inappropriate antibiotic use include delayed prescriptions, patient education, and calling the infection a chest cold.
Geokas, Michael C.
For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467
Emeksiz, Serhat; Kutlu, Nurettin Onur; Çaksen, Hüseyin; Alkan, Gülsüm; Yıkmaz, Hülya Şeker; Tokgöz, Hüseyin
Posterior reversible encephalopathy syndrome is characterized by hypertension, seizure, headache, clouding of consciousness, and visual disturbance, and is diagnosed in the presence of typical lesions on magnetic resonance imaging. We retrospectively evaluated five patients who were diagnosed as having posterior reversible encephalopathy syndrome and followed up in Meram Medical Faculty, Pediatric Intensive Care and Hematology wards, between January 2010 and January 2014. We reviewed the demographic and clinical data, and neuroimaging findings. The primary diseases of the subjects included acute lymphocytic leukemia (n=2), Henoch-Schönlein purpura (n=1), systemic lupus erythematous (n=1), and acute poststreptococcal glomerulonephritis (n=1). The mean age was 10±4.58 years (range, 5–14 years). Acute elevation of blood pressure was found in all patients (n=5). Initial neurologic manifestations included seizure, clouding of consciousness, headache, and visual disturbance. After the diagnosis was made through clinical evaluations and magnetic resonance imaging, complete clinical recovery was obtained in all patients with the appropriate therapeutic approach. In conclusion, posterior reversible encephalopathy syndrome should be considered in the differential diagnosis of patients who present with encephalopathy and underlying diseases such as nephritis, vasculitis, malignancy accompanied by hypertension, and a history of use of medication. PMID:28123335
The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835
Meekins, Jessica M
Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.
Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1−5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides, different doses [amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides], long-course regimens), antihistamines, cephalosporins or macrolides, decongestants (xylometazoline, phenylephrine, pseudoephedrine), doxycycline, saline nasal washes, steam inhalation, and topical corticosteroids (intra-nasal). PMID:19450327
Barr, Wendy; Smith, Andrew
Acute diarrhea in adults is a common problem encountered by family physicians. The most common etiology is viral gastroenteritis, a self-limited disease. Increases in travel, comorbidities, and foodborne illness lead to more bacteria-related cases of acute diarrhea. A history and physical examination evaluating for risk factors and signs of inflammatory diarrhea and/or severe dehydration can direct any needed testing and treatment. Most patients do not require laboratory workup, and routine stool cultures are not recommended. Treatment focuses on preventing and treating dehydration. Diagnostic investigation should be reserved for patients with severe dehydration or illness, persistent fever, bloody stool, or immunosuppression, and for cases of suspected nosocomial infection or outbreak. Oral rehydration therapy with early refeeding is the preferred treatment for dehydration. Antimotility agents should be avoided in patients with bloody diarrhea, but loperamide/simethicone may improve symptoms in patients with watery diarrhea. Probiotic use may shorten the duration of illness. When used appropriately, antibiotics are effective in the treatment of shigellosis, campylobacteriosis, Clostridium difficile, traveler's diarrhea, and protozoal infections. Prevention of acute diarrhea is promoted through adequate hand washing, safe food preparation, access to clean water, and vaccinations.
Repeated subcutaneous (SC) injections of mercuric chloride (MC) in Brown Norway (BN) rats induce an autoimmune glomerulonephritis (GN) due to antiglomerular basement membrane (BM) antibody deposition in the glomeruli. The aim of this study was to investigate the effects on MC-induced autoimmune GN of OKY-046, a selective TXA-synthetase inhibitor herring oil (HO), which is rich in eicosapentaenoic acid (EPA) (5.6%) precursor of the three series of prostaglandins (PGs) and of (inactive) thromboxane (TXA3), and evening primrose oil (EPO), which is rich in linoleic acid (LA) (72%) and gamma-linolenic acid (GLNA) (9%), precursors of the one series of PGs, mainly PGE1, and of (inactive) TXA1. The administration of OKY-046 significantly inhibited proteinuria, partially prevented fibrin thrombi (FT) formation in the glomeruli, decreased urinary TXB, enhanced 6ketoPGF excretion and, increased survival rate of the animals from 60% (group receiving only MC) to 86%. However, OKY-046 did not prevent body weight (BW) loss or the development and deposition of IgG in the glomeruli. Increased intake of HO (80 days prior and throughout the experiment) and avoidance of arachidonic acid (AA) intake produced an effect comparable to that of OKY-046 in the rats. Furthermore, HO significantly inhibited the deposition of IgG in the glomeruli, increased the survival rate of the animals to 100% and further enhanced the increased urinary PGE excretion induced by MC. However, HO did not prevent BW loss in the animals. Increased intake of EPO and avoidance of AA intake produced an effect comparable to that of HO. Additionally, EPO completely prevented BW loss induced by MC in these animals. These findings suggest that the metabolites of AA, EPA and GLNA play an important role either in the development or in the modulation of this model of MC induced GN.
Tuganbekova, Saltanat; Gaipov, Abduzhappar; Turebekov, Zaiyrkhan; Saparbayev, Samat; Shaimardanova, Galiya; Popova, Nadezhda; Taubaldiyeva, Zhannat; Serebrennikova, Dina; Trimova, Rakhat
Proteinuria is a major cause of glomerulosclerosis progression in glomerular diseases, and the development of end-stage renal disease is more rapid in nephrotic patients than in nonnephrotic ones. The renal parenchyma is less regenerable because it is a tissue consisting of renal cells. Thus, stem cells obtained from fetal kidney tissue might be effective for reducing proteinuria and delaying glomerulosclerosis in these patients. This report presents preliminary data from a prospective cohort study that included 17 patients with chronic glomerulonephritis in stage 2 to 4 chronic kidney disease who completed 3 visits during 1 year of follow-up. Fetal renal stem cells (multiple cells in suspension) were injected into the patient every 6 months. Patients were divided into 2 groups according to their nephrotic status, and 24-hour maximal proteinuria was recorded for at least 6 months (first group with proteinuria < 3.5 g/24 h, and second group with proteinuria > 3.5 g/24 h). During follow-up, group 1 was observed to have stable hemoglobin and total protein levels but significantly decreased albumin levels and glomerular filtration rates. In group 2, total protein with serum albumin significantly increased, and proteinuria and glomerular filtration rates significantly decreased. There was no significant difference in glomerular filtration rate decline between groups. Treatment with fetal renal stem cells significantly decreased proteinuria in nephrotic patients. However, this outcome also might have resulted from a reduction in glomerular filtration rate. Further studies with a larger number of patients and a control group would help to achieve better results that measure the efficacy of this treatment.
Hachmo, Yafit; Kalechman, Yona; Skornick, Itai; Gafter, Uzi; Caspi, Rachel R.; Sredni, Benjamin
Crescentic glomerulonephritis (CGN) is the most aggressive form of GN and, if untreated, patients can progress to end-stage renal failure within weeks of presentation. The α4β1 integrin very late antigen-4 (VLA-4) is an adhesion molecule of fundamental importance to the recruitment of leukocytes in inflammation. We addressed the role of VLA-4 in mediating progressive renal injury in a rat model of CGN using a small tellurium compound. AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate]. This compound has been previously shown to uniquely inhibit VLA-4 activity by redox inactivation of adjacent thiols in the exofacial domain of VLA-4. The study shows that administration of AS101 either before or after glomerular basement membrane anti-serum injection ameliorates crescent formation or preserves renal function. This was associated with profound inhibition of critical inflammatory mediators, accompanied by decreased glomerular infiltration of macrophages. Mechanistic studies demonstrated vla-4 inactivation on glomerular macrophages both in vitro and in vivo as well as inhibition of caspase-1 activity. Importantly, this cysteine protease activity modification was dependent on VLA-4 inactivation and was associated with the anti-inflammatory activity of AS101. We propose that inactivation of macrophage VLA-4 by AS101 in vivo results in a decrease of inflammatory cytokines and chemokines produced in the glomeruli of diseased rats, resulting in decreased further macrophage recruitment and decreased extracellular matrix expansion. Thus, AS101, which is currently in clinical trials for other indications, might be beneficial for treatment of CGN. PMID:28326083
Wu, Jean; Zhou, Cindy; Robertson, Julie; Carlock, Colin; Lou, Ya-Huan
In an anti-glomerular basement membrane (GBM) glomerulonephritis (GN) model, GN-resistant Lewis rats naturally recover from early glomerular inflammation. Here we investigated recovery mechanisms for development of a potential immunotherapy for autoimmune GN. Our previous studies suggested that glomeruli-infiltrating leukocytes with a phenotype of CD8αα+CD11c+MHC-II+CD3- (GIL CD8αα+ cells) were responsible for recovery through induction of T-cell apoptosis. Now, we identified peripheral blood CD8αα+CD11c+MHC-II+CD3- cells (PBMC CD8αα+CD3- cells), which shared 9 markers with GIL CD8αα+ cells. Upon incubation, PBMC CD8αα+CD3- cells displayed a morphology resembling that of dendritic cells. Similar to GIL CD8αα+ cells, PBMC CD8αα+CD3- cells were capable of inducing T-cell apoptosis in vitro. Hence, PBMC CD8αα+CD3- cells were likely the precursor of GIL CD8αα+ cells. We next tested their potential in vivo function. PBMC CD8αα+CD3- cells were able to infiltrate inflamed but not normal glomeruli. Isolated PBMC CD8αα+CD3- cells of Lewis rats were transferred into GN-prone Wistar-Kyoto rats at early inflammatory stage (days 17-25). When examined at day 45, both histopathology and blood urea nitrogen/serum creatinine level showed significantly attenuated GN in 80% of cell recipient Wistar-Kyoto rats. Separate experiments verified infiltration of transferred Lewis PBMC CD8αα+CD3- into the glomeruli, accompanied with apoptotic CD4+ T cells in the glomeruli of the recipient Wistar-Kyoto rats. Thus, PBMC CD8αα+CD3- cells of Lewis rats were able to terminate ongoing autoimmune inflammation in the glomeruli.
Ersdal, C; Jørgensen, H J; Lie, K-I
Polyarthritis caused by Erysipelothrix rhusiopathiae is a relatively common infection in lambs characterized by low mortality and high morbidity. E. rhusiopathiae is a ubiquitous Gram-positive bacterium that is both a commensal and a pathogen of vertebrates. The disease was studied during an outbreak in a Norwegian Spæl sheep flock. In the acute phase, 48 of 230 (20%) lambs developed clinical signs and 4 died (1.7%). One acute case was necropsied and E. rhusiopathiae was cultured from all major organs investigated and from joints. There was a fibrinous polyarthritis, increased presence of monocytes in vessels, and necrosis of Purkinje cells. Sixteen of the diseased animals (33%) developed a chronic polyarthritis. Eight of these lambs were necropsied; all had lesions in major limb joints, and 3 of 8 also had lesions in the atlanto-occipital joint. At this stage, E. rhusiopathiae was cultured only from the joints in 7 of 8 (87.5%) lambs, but by real-time polymerase chain reaction, we showed persistence of the bacterium in several organs. Pulsed-field gel electrophoresis typing of the bacterial isolates indicated that the same strain caused the acute and chronic disease. Five of 6 (83%) chronically affected animals had amyloidosis of the spleen, and 6 of 8 (75%) had amyloidosis of the liver. All chronically affected animals had a glomerulonephritis, and 6 of 8 (75%) had sparse degeneration in the brain. Ceruloplasmin and haptoglobin were significantly increased in the chronically diseased lambs. These results show that chronic ovine erysipelas is not restricted to joints but is a multisystemic disease.
Ramasastry, Sai S
The most important factors in the management of acute wounds are the history and physical examination. The goals of wound care are fivefold: avoid further tissue damage, achieve wound closure as rapidly as possible, restore function to the injured tissue, facilitate the patient's expedient return to normal daily activities, and restore the patient's quality of life. The treating physician must have a good understanding of the wound healing mechanism. One must rule out all associated occult injuries that may be life threatening. Proper wound assessment and management with minimal discomfort to the patient are crucial. The primary goal is to facilitate the healing process to achieve a cosmetically pleasing and functional result.
Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor
SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436
Group A Streptococcus (GAS) infections cause substantial worldwide morbidity and mortality, mostly associated with suppurative complications such as pharyngitis, impetigo, and non-suppurative immune syndromes such as acute rheumatic fever, rheumatic heart disease, and acute post-streptococcal glomerulonephritis. Deaths occur mostly in children, adolescents, and young adults in particular pregnant women in low- and middle-income countries. GAS strains are highly variable, and a GAS vaccine would need to overcome the issue of multiple strains. Several approaches have been used multivalent vaccines using N-terminal polypeptides of different M protein; conserved M protein vaccines with antigens from the conserved C-repeat portion of the M protein; incorporation selected T- and B-cell epitopes from the C-repeat region in a synthetic polypeptide or shorter single minimal B-cell epitopes from this same region; and non-M protein approaches utilizing highly conserved motives of streptococcal C5a peptidase, GAS carbohydrate and streptococcal fibronectin-binding proteins. A GAS vaccine represents urgent need for this neglected disease and should therefore deserve the greatest attention of international organizations, donors, and vaccine manufacturers. PMID:27489799
Georgievskaya, Zhanna; Nowalk, Andrew J; Randhawa, Parmjeet; Picarsic, Jennifer
We report a case of a 21-year-old young man with underlying congenital heart disease who developed Bartonella henselae endocarditis of the right ventricular outflow tract (RVOT) conduit of his Melody transcatheter (percutaneous) pulmonary valve (TPV), with an initial presentation of glomerulonephritis with a dominant C3 pattern, with renal failure and circulating cryoglobulins. There are few reports of a glomerulonephritis with a dominant C3 pattern presenting as a manifestation of B. henselae endocarditis. While most cases of B. henselae endocarditis affect the aortic valve, in this case the valve damage was to the RVOT of the Melody TPV, a percutaneous transcatheter valve delivery system that had previously replaced his pulmonary homograft, which had become dysfunctional as a result of prior Streptococcus viridans endocarditis. The pulmonary homograft had been in place since childhood as a result of a Ross procedure to repair his congenital aortic stenosis. The patient's renal failure significantly improved after surgical resection of the infected RVOT and institution of appropriate antibiotic therapy.
A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years.
Pedersen, E B; Bech, J N; Nielsen, C B; Kornerup, H J; Hansen, H E; Spencer, E S; Sølling, J; Jensen, K T
The effects of an ACE-inhibitor (ramipril), a calcium antagonist (felodipine) and placebo on glomerular filtration rate (GFR), urinary albumin/creatinine ratio, blood pressure (BP) and vasoactive hormones were investigated in a randomized, prospective, double-blind, placebo-controlled study of patients with chronic glomerulonephritis and hypertension, with measurements at entrance and after 12 and 24 months. In total, 33 patients were included: 21 completed the study with 7 patients in each group. GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays. The reduction in GFR was significantly more pronounced in the felodipine group (-7 ml/min) than in the ramipril group (0 ml/min) but the same as in the placebo group (-6 ml/min). The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group (-74 mg/mmol) than in the placebo group (-11 mg/mmol), which did not deviate from the felodipine group (-10 mg/mmol). BP was significantly reduced by ramipril and felodipine, but not by placebo. Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups, but were unchanged in the ramipril group. Endothelin increased only in the placebo group, and vasopressin, atrial natriuretic peptide, and brain natriuretic peptide were not significantly changed in any of the groups. It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR.
[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].
Takeda, T; Takeda, T; Naiki, Y; Yonekawa, S; Sakaguchi, M; Iwamoto, I; Tanaka, H; Hasegawa, H; Imada, A; Kanamaru, A; Hiruma, S; Maekura, S; Hashimoto, S; Yamazumi, T
A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.
Baxter, G M
Laminitis is an inflammation of the sensitive laminae along the dorsal aspect of the digit and is considered to be a secondary complication of several predisposing or primary factors. Affected horses are usually very lame, have increased digital pulses, are painful to hoof testers along the toe of the foot, and have evidence of downward rotation or distal displacement of the distal phalanx present on radiographs. Treatments for acute laminitis include anti-inflammatory drugs, anti-endotoxin therapy, vasodilators, antithrombotic therapy, corrective trimming and shoeing, and surgical procedures. Treatment regimens are very controversial and the true efficacy of these treatments is unknown. The quality of laminae damage that occurs with laminitis, however, probably has greater influence on the success of treatment and outcome of the horse than the treatment regimen itself.
Chowdhary, Vaidehi R.; Dai, Chao; Tilahun, Ashenafi Y.; Hanson, Julie A.; Smart, Michele K.; Grande, Joseph P.; Rajagopalan, Govindarajan; Fu, Shu-Man; David, Chella S.
MHC, especially HLA-DR3 and HLA-DR2, is one of the most important genetic susceptibility regions for systemic lupus erythematosus. Human studies to understand the role of specific HLA alleles in disease pathogenesis have been hampered by the presence of strong linkage disequilibrium in this region. To overcome this, we produced transgenic mice expressing HLA-DR3 (DRβ1*0301) and devoid of endogenous class II (both I-A and I-E genes, AE0) on a lupus-prone NZM2328 background (NZM2328.DR3+AE0). Both NZM2328 and NZM2328.DR3+AE0 mice developed anti-dsDNA and glomerulonephritis, but anti-dsDNA titers were higher in the latter. Although kidney histological scores were similar in NZM2328 and NZM2328.DR3+AE0 mice (7.2 ± 4.3 and 8.6 ± 5.7, respectively, p = 0.48), the onset of severe proteinuria occurred earlier in NZM2328.DR3+AE0 mice compared with NZM2328 mice (median, 5 and 9 mo respectively, p < 0.001). Periarterial lymphoid aggregates, classic wire loop lesions, and occasional crescents were seen only in kidneys from NZM2328.DR3+AE0 mice. Interestingly, NZM2328.DR3+AE0 mice, but not NZM2328 mice, spontaneously developed anti-Smith (Sm) Abs. The anti-Sm Abs were seen in NZM2328.DR3+AE0 mice that were completely devoid of endogenous class II (AE−/−) but not in mice homozygous (AE+/+) or heterozygous (AE+/−) for endogenous MHC class II. It appears that only HLA-DR3 molecules can preferentially select SmD-reactive CD4+ T cells for generation of the spontaneous anti-Sm immune response. Thus, our mouse model unravels a critical role for HLA-DR3 in generating an autoimmune response to SmD and lupus nephritis in the NZM2328 background. PMID:26475924
Chowdhary, Vaidehi R; Dai, Chao; Tilahun, Ashenafi Y; Hanson, Julie A; Smart, Michele K; Grande, Joseph P; Rajagopalan, Govindarajan; Fu, Shu-Man; David, Chella S
MHC, especially HLA-DR3 and HLA-DR2, is one of the most important genetic susceptibility regions for systemic lupus erythematosus. Human studies to understand the role of specific HLA alleles in disease pathogenesis have been hampered by the presence of strong linkage disequilibrium in this region. To overcome this, we produced transgenic mice expressing HLA-DR3 (DRβ1*0301) and devoid of endogenous class II (both I-A and I-E genes, AE(0)) on a lupus-prone NZM2328 background (NZM2328.DR3(+)AE(0)). Both NZM2328 and NZM2328.DR3(+)AE(0) mice developed anti-dsDNA and glomerulonephritis, but anti-dsDNA titers were higher in the latter. Although kidney histological scores were similar in NZM2328 and NZM2328.DR3(+)AE(0) mice (7.2 ± 4.3 and 8.6 ± 5.7, respectively, p = 0.48), the onset of severe proteinuria occurred earlier in NZM2328.DR3(+)AE(0) mice compared with NZM2328 mice (median, 5 and 9 mo respectively, p < 0.001). Periarterial lymphoid aggregates, classic wire loop lesions, and occasional crescents were seen only in kidneys from NZM2328.DR3(+)AE(0) mice. Interestingly, NZM2328.DR3(+)AE(0) mice, but not NZM2328 mice, spontaneously developed anti-Smith (Sm) Abs. The anti-Sm Abs were seen in NZM2328.DR3(+)AE(0) mice that were completely devoid of endogenous class II (AE(-/) (-)) but not in mice homozygous (AE(+/+)) or heterozygous (AE(+/-)) for endogenous MHC class II. It appears that only HLA-DR3 molecules can preferentially select SmD-reactive CD4(+) T cells for generation of the spontaneous anti-Sm immune response. Thus, our mouse model unravels a critical role for HLA-DR3 in generating an autoimmune response to SmD and lupus nephritis in the NZM2328 background. Copyright © 2015 by The American Association of Immunologists, Inc.
Hui, Charles Ps
Acute otitis externa, also known as 'swimmer's ear', is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.
Hui, Charles PS
Acute otitis externa, also known as ‘swimmer’s ear’, is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present. PMID:24421666
Parra, G.; Takekoshi, Y.; Striegel, J.; Vernier, R. L.; Michael, A. F.
Acute serum sickness was induced in New Zealand White (NZW) and in C6 deficient (C6D) rabbits, to compare the histology, immunofluorescence, especially distribution of poly C9 (MAC), and electron microscopic characteristics of the disease in each strain. Glomerulonephritis and albuminuria of comparable extent occurred in 13/17 NZW and 4/8 C6D rabbits. In NZW rabbits with albuminuria an early intense glomerular infiltration by mononuclear cells was associated with focal small fine granular glomerular basement membrane (GBM) deposits of IgG and BSA and more diffuse and larger deposits of C3 and MAC. After the disappearance of monocytes and decrease in mesangial cell proliferation, development of large subepithelial GBM deposits rich in all immune reactants was observed in NZB rabbits. In C6D rabbits with albuminuria a similar monocytic infiltrate occurred, but no association with IgG and C3 GBM immune deposits was noted. No deposits of MAC and no large subepithelial GBM 'humps' were observed in C6D rabbits. We conclude that the exudative (monocytic) phase of glomerular injury and albuminuria in acute serum sickness nephritis are not dependent upon terminal complement components, but the subsequent formation of large subepithelial GBM deposits does not occur in this model in the absence of MAC. Images Fig. 2 Fig. 3 Fig. 4 PMID:1622842
Adike, Abimbola; Cherry, Mariyam; Awar, Melina
IgM nephropathy is a relatively rare cause of idiopathic nephrotic syndrome.1 It was initially described by van de Putte,2 then by Cohen and Bhasin in 1978, as a distinctive feature of mesangial proliferative glomerulonephritis.2 It is typically characterized by diffuse IgM deposits on the glomeruli and diffuse mesangial hypercellularity. Little is known about the pathogenesis and treatment of this disease.1,3 We describe a patient who presented with nonspecific symptoms of epigastric pain, nausea, and early satiety. Abdominal imaging and endoscopies were unremarkable. She was found to have significant proteinuria (6.4 g/24 hours), hyperlipidemia, and edema consistent with a diagnosis of nephrotic syndrome. Kidney biopsy was performed and confirmed an IgM nephropathy. Less than 2 weeks after her diagnosis of IgM nephropathy, she presented with an acute cerebellar stroke. Thrombophilia is a well-known complication of nephrotic syndrome, but a review of the literature failed to show an association between IgM nephropathy and acute central nervous system thrombosis. PMID:27057296
Malbora, Baris; Bilaloglu, Eris
The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.
Heukelbach, Jörg; Feldmeier, Hermann
Scabies is a neglected parasitic disease that is a major public health problem in many resource-poor regions. It causes substantial morbidity from secondary infections and post-infective complications such as acute post-streptococcal glomerulonephritis. Disease control requires treatment of the affected individual and all people they have been in contact with, but is often hampered by inappropriate or delayed diagnosis, poor treatment compliance, and improper use of topical compounds such as permethrin, lindane, or benzyl benzoate. In addition to concerns over toxicity with such compounds, parasite resistance seems to be increasing. Oral ivermectin is an alternative that has been used successfully in community control programmes. Plant derivatives such as turmeric, neem, and tea tree oil are also promising future treatments. The disease is strongly associated with poverty and overcrowding, and the associated stigma can ostracise affected individuals. Treatment of scabies in poor countries needs to integrate drug treatment programmes with efforts to improve the socioeconomic conditions and education programmes to reduce stigma. We expect the future to bring more sensitive and specific clinical and laboratory-based diagnostic methods, as well as new therapeutic strategies.
Heukelbach, Jorg; Mazigo, Humphrey D; Ugbomoiko, Uade S
Features of endemic scabies are specific in resource-poor and underprivileged communities, with implications for control measures on the community level. In this review, these special aspects are addressed. Scabies is endemic in many resource-poor communities, with a prevalence of 20% and higher. Transmission is influenced by social attitudes, migration, access to healthcare services, housing conditions, hygiene conditions, and crowding. Endemic scabies occurs with severe infestations, complications, and sequels, mainly in children. Sleep loss as a result of scabies-related itching is common. Complications include secondary infections by group A streptococci and acute poststreptococcal glomerulonephritis. Shame, restriction of leisure activities, and stigmatization are common. Treatment of scabies includes a variety of topical compounds, but control on the community level is not an easy task. As ivermectin kills a variety of other parasites, this oral drug is increasingly used for mass treatment. Intervention should address socioemotional aspects using an integrated approach with professionals from different areas, and the community. Scabies is a neglected disease and needs to be perceived as an important public health problem causing morbidity in many resource-poor communities. Future work on epidemiology, clinical aspects, transmission dynamics, socioeconomic aspects, and sustainable control in resource-poor communities is needed.
Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)
Lee, V K; Kimbrough, D J; Jarquin-Valdivia, A A
Acute bacterial parotitis (ABP) is a relatively uncommon condition that tends to occur in debilitated older patients. We report a case of an older woman that presented with an acute intracerebral hemorrhage who developed ABP. This morbidity led to endotracheal intubation, mechanical ventilation, tracheostomy and gastrostomy, all of which were not initially needed. We discuss the proposed physiopathology and etiopathogenesis of ABP in adults.
... treatment of acute lymphoblastic leukemia in children. In: Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa.: ... et al. Acute lymphoblastic leukemia in adults. In: Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa.: ...
Monfared, Ali; Habibzadeh, Seyed Mahmoud; Mesbah, Seyed Alireza
We present acute phosphate nephropathy in a 28-year-old man, which was developed after a car accident due to rhabdomyolysis. Treatment of acute kidney injury was done with administration of sodium bicarbonate.
Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...
Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...
Kim, Ki Up; Kim, Jin Kyeung; Won, Jong Ho; Hong, Dae Sik; Park, Hee Sook; Park, Kyeung Kyu
The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immunesuppression. Leukemic patients, who presented significant RLQ pain, had been indicated for operation, despite having advanced disease or having had received chemotherapy or steroids. Four adult leukemia patients, complicated by acute appendictis, were reviewed. Two patients were in induction chemotherapy, one receiving salvage chemotheapy due to relapse and the other was in conservative treatment. Two patients were acute myelocytic leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had aleukemic leukemia. All patients underwent appendectomy and recovered without complication. Our experience supports the theory that the surgical management of appendicitis in acute leukemia is the most effective way, in spite of leukopenia. PMID:8268146
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. CURRENTOPINION Acute traumatic coagulopathy ...bleeding. The recognition of acute traumatic coagulopathy as a distinct clinical entity characterized by early coagulation dysfunction, arising prior to...traumatic coagulopathy . Recent findings We focus on recent advances in the mechanistic understanding of acute traumatic coagulopathy , particularly
Jardin, François; Vieillard-Baron, Antoine
Acute cor pulmonale is a form of acute right heart failure produced by a sudden increase in resistance to blood flow in the pulmonary circulation, which is now rapidly recognized by bedside echocardiography. In the clinical setting, acute cor pulmonale is mainly observed as a complication of massive pulmonary embolism or acute respiratory distress syndrome. In acute respiratory distress syndrome, the worsening effect of mechanical ventilation has been recently emphasized. As a general rule, the treatment consists in rapidly reducing resistance to blood flow in the pulmonary circulation, obtained by a specific strategy according to etiology.
Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo
Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness.
Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia
Wald, Ellen R
Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.
From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barré syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies.
Matsuo, Nanae; Yamamoto, Hiroyasu; Kobayashi, Akimitsu; Yamamoto, Izumi; Mitome, Jun; Maruyama, Yukio; Hayakawa, Hiroshi; Miyazaki, Yoichi; Utsunomiya, Yasunori; Hosoya, Tatsuo; Yamaguchi, Yutaka
A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis underwent kidney transplantation from a living unrelated spousal donor. The blood type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6 locus mismatch. She had become pregnant twice by her donor and had never received blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She initially underwent one week of immunosuppression with mycophenolate mofetil (MMF) and double filtration plasmapheresis (DFPP) immediately before transplantation to reduce the risk of antibody-mediated rejection. Induction therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and basiliximab. The allograft function was excellent immediately after the operation. However, the urine output and platelet count declined rapidly on post-operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase levels rose gradually. Subsequently, we could not detect the diastolic arterial flow on Doppler sonography. We diagnosed accelerated acute rejection and treated her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The first episode biopsy on POD 7 revealed acute vascular rejection and acute antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased beginning on POD 13, while the sCr level decreased gradually and reached 0.9 mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor-specific antibody (DSA). This case suggested that, for successful kidney transplantation in highly sensitized recipients, such as husband-to-wife spousal kidney transplantation with a history of pregnancy, we should keep the risk of AMR in mind, even if the sensitive antibody detection tests are negative.
Naqvi, Rubina; Mubarak, Muhammed; Ahmed, Ejaz; Akhtar, Fazal; Bhatti, Sajid; Naqvi, Anwar; Rizvi, Adib
Introduction: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. Objectives: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. Patients and Methods: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. Results: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. Conclusion: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome. PMID:26693497
Maier, Alexander; Kommer, Vera
We report on a young women with acute rheumatic fever. Acute rheumatic fever has become a rare disease in Germany, especially in adults. This carries the risk that it can be missed in the differential diagnostic considerations of acute rheumatic disorders and febrile status. If rheumatic fever is not diagnosed and treated correctly, there is a considerable risk for rheumatic valvular heart disease. In this article diagnosis, differential diagnosis and therapy of rheumatic fever are discussed extensively.
Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel
Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569
Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.
A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337
Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.
Strauss, J; Pardo, V; Koss, M N; Griswold, W; McIntosh, R M
The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.
Comparison of clinical and laboratory parameters in patients with end-stage renal failure in the outcome of chronic glomerulonephritis and patients with end-stage renal failure in the outcome of other diseases.
Popova, J A; Yadrihinskaya, V N; Krylova, M I; Sleptsovа, S S; Borisovа, N V
frequent complications of hemodialysis treatments are coagulation disorders. This is due to activation of the coagulation of blood flow in the interaction with a dialysis membrane material vascular prostheses and extracorporeal circuit trunks. In addition, in hemodialysis patients receiving heparin for years, there is depletion of stocks in endothelial cells in tissue factor inhibitor, inhibits the activity of an external blood clotting mechanism. the aim of our study was to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure. to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure and hemodialysis treatment duration conducted a study that included 100 patients observed in the department of chronic hemodialysis and nephrology hospital №1 Republican National Medical Center in the period of 2013-2016. in patients with end-stage renal failure in the outcome of chronic glomerulonephritis, a great expression of activation of blood coagulation confirm increased the mean concentration of fibrinogen, whereas in the group, which included patients with end-stage renal failure in the outcome of other diseases, such is not different from the norm, and a higher rate of hyperfibrinogenemia, identified in 2/3 patients in this group. it was revealed that the state of homeostasis in patients with end-stage renal failure in increasingly characterizes the level of fibrinogen and the activation of the hemostatic markers: soluble fibrin monomer complexes, D-dimers.
Deposition of alpha 1-antitrypsin and loss of glycoconjugate carrying Ulex europaeus agglutinin-I binding sites in the glomerular sclerotic process. Phenomena common to chronic pyelonephritis and chronic diffuse proliferative glomerulonephritis.
Yonezawa, S; Irisa, S; Nakamura, T; Uemura, S; Otsuji, Y; Ohi, Y; Sato, E
Sclerotic processes of glomeruli in chronic pyelonephritis (CPN) and chronic diffuse proliferative glomerulonephritis (CDPGN) were investigated in a lectin binding study in connection with an immunofluorescent examination of protease inhibitor deposition. Ulex europaeus agglutinin-I (UEA-I), which is specific to a certain terminal alpha-L-fucosyl residue of glycoconjugates, specifically labelled intact endothelia of glomerular capillaries, peritubular capillaries and blood vessels in human kidneys. Segmental or global loss of the UEA-I binding with glomerular capillaries was observed in the sclerotic areas where alpha 1-antitrypsin (alpha 1AT) deposits were always detected in the glomeruli with segmental or global sclerosis of CPN. This high correlation between loss of UEA-I binding and alpha 1AT deposition was also observed in the affected glomeruli of CDPGN. In considering glomerular sclerosis, it is significant that loss of UEA-I binding and alpha 1AT deposition are common to both CPN and CDPGN, although their original etiologies are quite different.
Gray, Matthew Philip; Gorelick, Marc H
Acute disseminated encephalomyelitis is a primarily pediatric, immune-mediated disease characterized by demyelination and polyfocal neurologic symptoms that typically occur after a preceding viral infection or recent immunization. This article presents the pathophysiology, diagnostic criteria, and magnetic resonance imaging characteristics of acute disseminated encephalomyelitis. We also present evaluation and management strategies.
Atkinson, K.; Wells, D. G.; Clink, H. McD.; Kay, H. E. M.; Powles, R.; McElwain, T. J.
Seventy-eight adult patients with acute leukaemia were classified cytologically into 3 categories: acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML) or acute undifferentiated leukaemia (AUL). The periodic acid-Schiff stain was of little value in differentiating the 3 groups. The treatment response in each group was different: 94% of patients with ALL (16/17) achieved complete remission with prednisone, vincristine and other drugs in standard use in childhood ALL; 59% of patients with AML (27/46) achieved complete remission with cytosine arabinoside and daunorubicin (22 patients), or 6-thioguanine and cyclophosphamide (2 patients), 6-thioguanine, cyclophosphamide and Adriamycin (1 patient), and cytosine and Adriamycin (1 patient); only 2 out of 14 patients (14%) with acute undifferentiated leukaemia achieved complete remission using cytosine and daunorubicin after an initial trial of prednisone and vincristine had failed. Prednisone and vincristine would seem to be of no value in acute undifferentiated leukaemia. It would seem also that no benefit is obtained by classifying all patients with acute leukaemia over 20 years of age as “adult acute leukaemia” and treating them with the same polypharmaceutical regimen. The problems posed by each disease are different and such a policy serves only to obscure them. ImagesFig. 1Fig. 2Fig. 3 PMID:4141625
Van Hook, James W
Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.
Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.
Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K
MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.
Bissell, D. Montgomery; Wang, Bruce
The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID:26357631
Acute renal failure (now acute kidney injury) is a common complication of critical illness affecting between 30 and 60% of critically ill patients. The development of a consensus definition (RIFLE--risk, injury, failure, loss, end-stage system) has allowed standardization of reporting and epidemiological work. Multicenter multinational epidemiological studies indicate that sepsis is now the most common cause of acute renal failure in the intensive care unit (ICU) followed by cardiac surgery-associated acute kidney injury. Unfortunately, our understanding of the pathogenesis of acute renal failure in these settings remains limited. Because of such limited understanding, no reproducibly effective therapies have been developed. In addition the diagnosis of acute renal failure still rests upon the detection of changes in serum creatinine, which only occur if more than 50% of glomerular filtration is lost and are often delayed by more than 24 hours. Such diagnostic delays make the implementation of early therapy nearly impossible. In response to these difficulties, there has been a concerted effort to use proteomics to identify novel early biomarkers of acute renal failure. The identification and study of neutrophil gelatinase- associated lipocalin has been an important step in this field. Another area of active interest and investigation relates to the role of intravenous fluid resuscitation and fluid balance. Data from large observational studies and randomized, controlled trials consistently indicate that a positive fluid balance in patients with acute renal failure represents a major independent risk factor for mortality and provides no protection of renal function. The pendulum is clearly swinging away from a fluid-liberal approach to a fluid-conservative approach in these patients. Finally, there is a growing appreciation that acute renal failure may identify patients who are at increased risk of subsequent chronic renal dysfunction and mortality, opening the way
... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...
... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...
Mason, Christopher; Dooley, Nessa; Griffiths, Mark
Acute respiratory distress syndrome is a common cause of acute respiratory failure that is underdiagnosed both inside and outside of intensive care units. Progression to the most severe forms of the syndrome confers a mortality rate greater than 40% and is associated with often severe functional disability and psychological sequelae in survivors. While there are no disease-modifying pharmacotherapies for the syndrome, this progression may be prevented through the institution of quality improvement measures that minimise iatrogenic injury associated with acute severe illness. © Royal College of Physicians 2017. All rights reserved.
Powell, Jessica; Graham, David; O'Reilly, Sarah; Punton, Gillian
Acute pulmonary oedema is a distressing and life-threatening illness that is associated with a sudden onset of symptoms. For the best possible patient outcomes, it is essential that nurses in all clinical areas are equipped to accurately recognise, assess and manage patients with acute pulmonary oedema. This article outlines the pathophysiology of acute cardiogenic and non-cardiogenic pulmonary oedema, and suggests a systematic approach to the recognition and management of its most serious manifestations. Long-term care and symptom recognition are discussed and suggestions for ongoing patient self-management are provided.
... occur with more severe acute mountain sickness include: Blue color to the skin (cyanosis) Chest tightness or congestion Confusion Cough Coughing up blood Decreased consciousness or withdrawal from social interaction Gray ...
Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora
Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers.
... cause acute liver failure include the poisonous wild mushroom Amanita phalloides, which is sometimes mistaken for one ... also can spread infection. Don't eat wild mushrooms. It can be difficult to tell the difference ...
Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.
... the Healthcare Professionals area of our site. PBS Documentary AIP Diagnosis Stories **Diagnostic Testing for the Acute ... treating AIP are based upon experience and clinical study. Since many commonly used drugs have not been ...
... movement due to disease or injury to the cerebellum in the brain. ... of acute cerebellar ataxia include: Abscess of the cerebellum Alcohol, medications, and insecticides Bleeding into the cerebellum ...
... drugs and anticonvulsants, can cause acute liver failure. Herbal supplements. Herbal drugs and supplements, including kava, ephedra, skullcap ... over-the-counter medications do you take? What herbal supplements do you take? Do you use illegal drugs? ...
Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora
Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers. PMID:24473429
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Brix, Silke; Stahl, Rolf
Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.
Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi
Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.
Whitehall, John; Kuzulugil, Deniz; Sheldrick, Kyle; Wood, Angela
The study aims to assess the health burden of children admitted with 'scabies' to Mt Isa Hospital, the referral centre for North West Queensland, from 2006 to 2010. This is a retrospective chart audit of admissions of children with 'scabies' including age, sex, date, residence, Indigenous status, result of skin swabs and length of stay, and the number of admissions with acute rheumatic fever (ARF) and acute post-streptococcal glomerulo-nephritis (APSGN) in that period. Financial burden was estimated from daily bed costs and transportation. There were 113 admissions with mean age of 23/12: 11% were <2/12 and mean stay was 4.5 days. 19 were admitted twice, 5 thrice and 2 four times. 7 individuals accounted for 25% of admissions. 'Scabies' accounted for 10.1% of medical admissions <5 years of age. Admissions increased from 10 in 2005 to 39 in 2010. The minimum cost per admission was $9584.07. Seventy-one per cent of swabs grew Group A streptococcus, all sensitive to penicillin. Sixty-three per cent of these were accompanied by Staphylococcus aureus, which was the sole organism in 18%. Sixty-four per cent of S. aureus were methicillin resistant. There were 29 admissions for ARF and 23 with APSGN. All children with 'scabies' and ARF and all but three with APSGN were Indigenous. Pyoderma and scabies are major health burdens in North West Queensland, requiring organised community-based prevention. The number of repeat admissions emphasises the futility of individual treatment. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
Desai, Jay; Mitchell, Wendy G
Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.
Bitar, Anas; Altaf, Muhammad; Sferra, Thomas J.
Summary Background: Pancreatitis in the pediatric age group is not as common as in adults. Etiologies are various and differ from those in adults. Although infectious etiology accounts for a significant number of cases of pancreatitis, acute infection with Human Immunodeficiency Virus (HIV) was rarely reported as a possible etiology for acute pancreatitis in adults. Acute pancreatitis has never been reported as a presenting manifestation of acute HIV infection in children. Case Report: We describe a pediatric patient who presented with acute pancreatitis that revealed acute HIV infection. Conclusions: Acute pancreatitis as a primary manifestation of HIV infection is very rare. It may represent an uncommon aspect of primary HIV infection. We suggest that acute HIV infection should be considered in the differential diagnosis of acute pancreatitis at all ages. PMID:23569476
Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi
Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.
McLean, Florence E
Scabies prevalence remains unacceptably high in many regions throughout the world. Infestation with scabies significantly impacts quality of life and is linked to pyoderma and consequently to severe long-term sequelae such as post-streptococcal glomerulonephritis. In the past, control programs using topical treatments have met with poor compliance; however, the highly effective oral agent ivermectin may offer a new paradigm in scabies management. Problems still exist with insensitive diagnostic tests, questions concerning mite reservoirs, and restrictions on who can receive ivermectin. Despite these difficulties, the elimination of scabies in communities worst affected may soon be possible.
Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia
Rodriguez, Eduardo A.; Lopez, Marvin A.; Valluri, Kartik; Wang, Danlu; Fischer, Andrew; Perdomo, Tatiana
Patient: Female, 43 Final Diagnosis: Myeloid sarcoma appendicitis Symptoms: Abdominal pain • chills • fever Medication: — Clinical Procedure: Laparoscopic appendectomy, bone marrow biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: The gastrointestinal tract is a rare site for extramedullary involvement in acute promyelocytic leukemia (APL). Case Report: A 43-year-old female with no past medical history presented complaining of mild abdominal pain, fever, and chills for the past day. On examination, she was tachycardic and febrile, with mild tenderness of her right lower quadrant and without signs of peritoneal irritation. Laboratory examination revealed pancytopenia and DIC, with a fibrinogen level of 290 mg/dL. CT of the abdomen showed a thickened and hyperemic appendix without perforation or abscess, compatible with acute appendicitis. The patient was given IV broad-spectrum antibiotics and was transfused with packed red blood cells and platelets. She underwent uncomplicated laparoscopic appendectomy and bone marrow biopsy, which revealed neo-plastic cells of 90% of the total bone marrow cellularity. Flow cytometry indicated presence of 92.4% of immature myeloid cells with t (15: 17) and q (22: 12) mutations, and FISH analysis for PML-RARA demonstrated a long-form fusion transcript, positive for APL. Appendix pathology described leukemic infiltration with co-expression of myeloperoxidase and CD68, consistent with myeloid sarcoma of the appendix. The patient completed a course of daunorubicin, cytarabine, and all trans-retinoic acid. Repeat bone marrow biopsy demonstrated complete remission. She will follow up with her primary care physician and hematologist/oncologist. Conclusions: Myeloid sarcoma of the appendix in the setting of APL is very rare and it might play a role in the development of acute appendicitis. Urgent management, including bone marrow biopsy for definitive diagnosis and urgent surgical intervention
Schreuder, Nanno; Mamedova, Ilahä; Jansman, Frank G A
The acute porphyrias are a group of rare metabolic disorders of the heme biosynthetic pathway. Carriers of the acute porphyria gene are prone to potentially fatal acute attacks, which can be precipitated by drug exposure. It is therefore important to know whether a drug is safe for carriers of the acute porphyria gene. In this study, radiopharmaceuticals were assessed on their porphyrogenicity (ie, the potential of a drug to induce an attack). The assessment was conducted by classifying the drugs according to the Thunell model. From 41 radiopharmaceuticals assessed, I-131 norcholesterol, Tc-99m mebrofenin, Tc-99m phytate, Tc-99m sestamibi, and Tl-201 chloride were classified as possibly porphyrogenic. I-131 norcholesterol, Tc-99m mebrofenin, Tc-99m phytate, Tc-99m sestamibi, and Tl-201 chloride should not be prescribed for patients experiencing acute porphyria unless an urgent indication is present and no safer alternative is available. In such cases, potential users should seek advice from a porphyria expert. Preventive measures may also be required. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
PARRA, G; HERNÁNDEZ, S; MORENO, P; RODRÍGUEZ-ITURBE, B
Bovine serum albumin (BSA) injected into the rabbits induces acute immune complex glomerulonephritis. Since albumin is filtered and reabsorbed in the tubules, we investigated whether tubulointerstitial cells participate in the pathogenesis of this experimental condition. For this purpose, we induced immune-complex nephritis in 45 rabbits with the injection of 125I-BSA and urinary BSA excretion, glomerular and tubulointerstitial BSA accumulation, lymphocyte infiltration, proliferative activity and MHC class II antigens were examined 2, 4–5 and 6–8 days after immunization. Proteinuria developed day 6–8. BSA was found in urine from day 2 (mean ± SE; 1089 ± 339 µg/24 h) and peaked on day 4 after immunization (2249 ± 1106). BSA content (cpm/g tissue) in tubulointerstitium (TI) and glomeruli were similar at day 2 (457 ± 45 and 407 ± 75, respectively), but afterward increased significantly in TI, reaching a peak level on day 5 (1026 ± 406) while remained unchanged in glomeruli (388 ± 95). At the same time, preceding the onset of proteinuria, maximal intensity of the lymphocyte infiltration, proliferative activity and MHC class II antigen expression in tubular cells, monocytes/macrophages and interstitial cells were observed. Our study shows that antigen is excreted in the urine and concentrated in TI in association with overexpression of MHC class II molecules and lymphocyte infiltration. These findings occur prior to the development of proteinuria and suggest that the tubulointerstitial cells play a critical role in the pathogenesis of this model. PMID:12823277
Abdominal pain is among the most frequent ailments reported in the office setting and can account for up to 40% of ailments in the ambulatory practice. Also, it is in the top three symptoms of patients presenting to emergency departments (ED) and accounts for 5-10% of all ED primary presenting ailments. There are several common sources for acute abdominal pain and many for subacute and chronic abdominal pain. This article explores the history-taking, initial evaluation, and examination of the patient presenting with acute abdominal pain. The goal of this article is to help differentiate one source of pain from another. Discussion of acute cholecystitis, pancreatitis, appendicitis, ectopic pregnancy, diverticulitis, gastritis, and gastroenteritis are undertaken. Additionally, there is discussion of common laboratory studies, diagnostic studies, and treatment of the patient with the above entities.
Cap, Andrew; Hunt, Beverley
Mortality from trauma remains a global public health challenge, with most preventable deaths due to bleeding. The recognition of acute traumatic coagulopathy as a distinct clinical entity characterized by early coagulation dysfunction, arising prior to medical intervention, has revolutionized trauma management over the last decade. The aim of this article is to review our current understanding of acute traumatic coagulopathy. We focus on recent advances in the mechanistic understanding of acute traumatic coagulopathy, particularly the changes in coagulation factors, physiological anticoagulants, endothelial activation, fibrinolysis and platelet dysfunction. Evolving diagnostic and therapeutic approaches are discussed, including viscoelastic coagulation monitoring and the role of tranexamic acid and blood products. Emphasis is now placed on early prevention, diagnosis, and aggressive initial treatment of coagulopathy and fibrinolysis with haemostatic blood products and tranexamic acid in addition to red cell units in order to reduce bleeding and improve clinical outcomes.
Dennert, Robert; Crijns, Harry J.; Heymans, Stephane
Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482
Boersma, Eric; Mercado, Nestor; Poldermans, Don; Gardien, Martin; Vos, Jeroen; Simoons, Maarten L
Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients.
Joseph, Susan M.; Cedars, Ari M.; Ewald, Gregory A.; Geltman, Edward M.; Mann, Douglas L.
Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure. PMID:20069075
Lukens, Francis D. W.; Longcope, Warfield T.
1. Both focal and diffuse glomerulitis has been produced in rabbits by the injection directly into the left renal artery of suspensions of heat killed hemolytic streptococci. 2. Similar lesions in the glomeruli could not be obtained by the injection of suspensions of bismuth oxychloride into the left renal artery of normal rabbits. 3. The acute glomerulitis occurred in only about one-half of the rabbits employed for the experiments. 4. Glomerulitis was observed much more frequently in rabbits in which an acute localized streptococcus infection had been produced by the intracutaneous injection of living hemolytic streptococci, than in normal rabbits. The occurrence of acute glomerulitis was usually associated with a well marked skin reaction to the filtrates of hemolytic streptococci. PMID:19869861
Migraine is one of the most frequent disabling neurological conditions with a major impact on the patient’s quality of life. Migraine has been described as a chronic disorder that characterized with attacks. Attacks are characterized by moderate–severe, often unilateral, pulsating headache attacks, typically lasting 4 to 72 hours. Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology. This article reviews management of migraine acute pharmacological treatment. Currently, for the acute treatment of migraine attacks, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (serotonin 5HT1B/1D receptor agonists) are recommended. Before intake of NSAID and triptans, metoclopramide or domperidone is useful. In very severe attacks, subcutaneous sumatriptan is first choice. The patient should be treated early in the attack, use an adequate dose and formulation of a medication. Ideally, acute therapy should be restricted to no more than 2 to 3 days per week to avoid medication overuse. PMID:28360580
Acute pancreatitis is an autodigestive disease in which the pancreatic tissue is damaged by the digestive enzimes produces by the acinar cells and is associated with severe upper abdominal pain. The severity of acute pancreatitis ranges from edema to necrosis of the gland. The edematous form of the disease occurs in about 80-85% of patients and is self-limited, with recovery in few days. In the 15-20% of patients with the most severe form of pancreatitis, hospitalization is prolonged and commonly associated with infection and other complications including multiple organ failure. The main causes of acute pancreatitis in adults are gallstones, other gallbladder (biliary) diseases and alcohol abuse. Treatment of acute pancreatitis-depends on the severity oft he condition. Generaly, the patients need, hospitalisation with administration of intravenous fluid to help restore blood volume, pain control, supplemental oxygen as required and correction of electrolite and metabolic abnormalities. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and sistemic infection. Begin oral feeding once abdominal pain has resolved and the patients regains appetite. The diet should be low in fat and protein. Patients suffering from infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. During recent years the management of acute pancreatitis has changed. This has been due particulary in response to the general availability of computed tomography, improved intensive care facilities, knowledge about the central role of pancreatic infection and refinements in surgical and other interventional techniques.
Introduction Low back pain affects about 70% of people in resource-rich countries at some point in their lives. Acute low back pain can be self-limiting; however, 1 year after an initial episode, as many as 33% of people still have moderate-intensity pain and 15% have severe pain. Acute low back pain has a high recurrence rate; 75% of those with a first episode have a recurrence. Although acute episodes may resolve completely, they may increase in severity and duration over time. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatments for acute low back pain? What are the effects of local injections for acute low back pain? What are the effects of non-drug treatments for acute low back pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, advice to stay active, analgesics (paracetamol, opioids), back exercises, back schools, bed rest, behavioural therapy, electromyographic biofeedback, epidural corticosteroid injections, lumbar supports, massage, multidisciplinary treatment programmes, muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), spinal manipulation, temperature treatments (short-wave diathermy, ultrasound, ice, heat), traction, and transcutaneous electrical nerve stimulation
Rolink, A.G.; Gleichmann, E.
Previous work from this laboratory has led to the hypothesis that the stimulatory pathological symptoms of chronic graft-vs.-host disease (GVHD) are caused by alloreactive donor T helper (TH) cells, whereas the suppressive pathological symptoms of acute GVHD are caused by alloreactive T suppressor (TS) cells of the donor. We analyzed the Lyt phenotypes of B10 donor T cells required for the induction of either acute or chronic GVHD in H-2-different (B10 X DBA/2)F1 recipients. When nonirradiated F1 mice were used as the recipients, we found unseparated B10 T cells induced only a moderate formation of systemic lupus erythematosus (SLE)-like autoantibodies, but a high percentage of lethal GVHD (LGVHD). In contrast, Lyt-1+2- donor T cells were unable to induce LGVHD in these recipients but were capable of inducing a vigorous formation of SLE-like autoantibodies and severe immune-complex glomerulonephritis. Lyt-1-2+ T cells were incapable of inducing either acute or chronic GVHD. The sensitivity and accuracy of the GVH system were increased by using irradiated F1 mice as recipients and then comparing donor-cell inocula that contained similar numbers of T lymphocytes. Donor-cell inocula were used that had been tested for their allohelper and allosuppressor effects on F1 B cells in vitro. In the irradiated F1 recipients unseparated donor T cells were superior to T cell subsets in inducing LGVHD. In contrast Lyt-1+2- T cells, but neither unseparated T cells nor Lyt-1-2+ T cells, were capable of inducing a vigorous formation of SLE-like auto-antibodies. We conclude that the stimulatory pathological symptoms of chronic GVHD are caused by Lyt-1+2- allohelper T cells. In contrast, the development of the suppressive pathological symptoms of acute GVHD appears to involve alloreactive Lyt-1+2+ T suppressor cells.
Acute rhinosinusitis is a common illness in children. Viral upper respiratory tract infection is the most common presentation of rhinosinusitis. Most children resolve the infection spontaneously and only a small proportion develops a secondary bacterial infection. The proper choice of antibiotic therapy depends on the likely infecting pathogens, bacterial antibiotic resistance, and pharmacologic profiles of antibiotics. Amoxicillin-clavulanate is currently recommended as the empiric treatment in those requiring antimicrobial therapy. Isolation of the causative agents should be considered in those who failed the initial treatment. In addition to antibiotics, adjuvant therapies and surgery may be used in the management of acute bacterial rhinosinusitis.
Birewar, Sonali; Oppenheimer, Mark; Zawada, Edward T
Muscular disorders and even hypothyroid myopathy with elevated muscle enzymes are commonly seen in hypothyroidism. In this paper, we report a case of acute renal failure in a 35-year old male patient with myalgia. His serum creatinine reached a level of 2.4 mg/dl. Later, his myalgia was found to be due to hypothyroidism with TSH of over 500 uiv/ml. With thyroid replacement therapy, myalgia and his serum creatinine stabilized and subsequently improved. Hypothyroidism, although rare, has been reported as a definite and authentic cause of rhabdomyolysis. As a result, hypothyroidism must be considered in patients presenting with acute renal failure and elevated muscle enzymes.
Newland, Catherine D
Pediatric acute liver failure (ALF) is a complex and rapidly progressive syndrome that results from a variety of age-dependent etiologies. It is defined by the acute onset of liver disease with no evidence of chronic liver disease. There must be biochemical or clinical evidence of severe liver dysfunction as defined by an international normalized ratio (INR) ≥2. If hepatic encephalopathy is present, INR should be ≥1.5. Unfortunately, due to the rarity of ALF in pediatric patients, there is a paucity of diagnostic and management algorithms and each patient must have an individualized approach. [Pediatr Ann. 2016;45(12):e433-e438.]. Copyright 2016, SLACK Incorporated.
Ramakrishnan, Kalyanakrishnan; Salinas, Robert C
Prostatitis, one of the most common urological infections afflicting adult men, has recently been divided into 4 different categories based on the National Institutes of Health consensus classification: acute bacterial prostatitis, chronic bacterial prostatitis, chronic nonbacterial prostatitis and pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Most patients with prostatitis are found to have either nonbacterial prostatitis or prostatodynia. Prostatitis poses an international health problem, with epidemiologic studies suggesting a worldwide prevalence of more than 10%. This article reviews current modes of diagnosis and therapy for acute and chronic prostatitis. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Nason, Katie S
Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk, and immediate management options by the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical.
Tamm, Alexander; Jeffery, Caroline C; Ansari, Khalid; Naik, Sandeep
We present a case of neck pain in a middle-aged woman, initially attributed to a retropharyngeal infection and treated with urgent intubation. With the help of computed tomography, the diagnosis was later revised to acute prevertebral calcific tendinitis, a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the longus colli muscles. It is critical to differentiate between these two disease entities due to dramatic differences in management. A discussion of acute prevertebral calcific tendinitis and its imaging findings is provided below.
Khurana, Vishal; Ganguly, Ishita
Recurrent acute pancreatitis (RAP) is commonly encountered, but less commonly understood clinical entity, especially idiopathic RAP, with propensity to lead to repeated attacks and may be chronic pancreatitis if attacks continue to recur. A great number of studies have been published on acute pancreatitis, but few have focused on RAP. Analysing the results of clinical studies focusing specifically on RAP is problematic in view due to lack of standard definitions, randomised clinical trials, standard evaluation protocol used and less post intervention follow-up duration. With the availability of newer investigation modalities less number of etiologies will remains undiagnosed. This review particularly is focused on the present knowledge in understanding of RAP.
Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur
Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.
Baydin, Ahmet; Nargis, Cemil; Nural, M Selim; Aygun, Dursun; Karatas, Aydin Deniz; Bahcivan, Muzaffer
Acute aortic dissection is an uncommon disease; however, it has a high mortality rate. Classically, aortic dissection presents with sudden and severe pain in the chest, back, or abdomen. Patients often describe tearing or ripping pain. There are a few reports of atypical findings or no pain in the literature. We report a case of painless, acute aortic dissection presenting as acute stroke.
Duvic, C; Nedelec, G; Debord, T; Herody, M; Didelot, F
Renal involvement in parasitic infections are polymorphic. Plasmodium malariae often leads to membranoproliferative glomerulonephritis whereas acute tubular necrosis or post-infectious acute glomerulonephritis are observed with Plasmodium falciparum. Urogenital taxis of Schistosoma haematobium is responsible for frequency of chronic tubular and interstitial nephritis. Without specific treatment, the renal function progressively deteriorates and urological complications appear. Schistosoma mansoni mainly leads to mesangial and membranoproliferative glomerulonephritis. Membranoproliferative and membranous glomerulonephritis are reported with loasis. Onchocerca volvulus also leads to membranoproliferative glomerulonephritis and lipoid nephrosis. Renal involvement with Wuchereria bancrofti is rare. With leishmaniosis, it is often mild but more serious observations are described: acute glomerulonephritis, nephrotic syndrome or acute interstitial nephritis. Renal hydatic cysts are diagnosed in two or three per cent of cases. Surgery is the only treatment. Immunosuppressive or antimalarial treatments seem to be ineffective in the outcome of chronic glomerulonephritis.
Hani, Mohamed Aziz; Guesmi, Fethi; Ben Achour, Jamel; Zribi, Riadh; Bouasker, Ibtissem; Zoghlami, Ayoub; Najah, Nabil
Among digestive clinical presentations of systemic lupus erythematosus, acute pancreatitis remains a serious affection with very poor prognosis. To date, pathogenesis is still unclear. We report two cases of fatal acute pancreatitis related to systemic lupus erythematosus.