Search

Chicken pox caused by varicella zoster virus is usually a self-limiting disease causing rare life-threatening complications. Involvement of the kidneys is infrequent during the course of the illness. Literature shows rare reports of acute glomerulonephritis following varicella infection. We report a case of 16-year-old boy presenting with anasarca with characteristic healed rashes of chicken pox. His urinalysis revealed a ‘massive’ nephrotic range proteinuria (16 g/24 hours), gross hematuria and pyuria. A percutaneous renal biopsy showed membranoproliferative glomerulonephritis. Most cases of post-varicella glomerulonephritis have been described in children, massive proteinuria of this range in an immunocompetent adolescent, being an extremely rare entity. Acute proliferative glomerulonephritis in such cases is usually an immune complex hypocomplementaemic glomerulonephritis in response to the zoster infection. Proteinuria in most patients is benign and self-limiting with few fatal reports of crescentic glomerulonephritis progressing to acute renal failure.

Background Small glomerular IgA deposits have been reported in patients with liver cirrhosis, mainly as an incidental finding in autopsy studies. We recently encountered nine cirrhotic patients who presented with acute proliferative glomerulonephritis with unusually large, exuberant glomerular immune complex deposits, in the absence of systemic lupus erythematosus (SLE) or monoclonal gammopathy-related kidney disease. Deposits were typically IgA dominant/codominant. Our aim was to further elucidate the etiology, diagnostic pitfalls, and clinical outcomes. Methods We present clinical features and kidney biopsy findings of nine cirrhotic patients with an unusual acute immune complex glomerulonephritis. We also identified native kidney biopsies from all patients with liver cirrhosis at our institution over a 13-year period (January 2004 to December 2016) to evaluate presence of glomerular IgA deposits in them (n = 118). Results Six of nine cirrhotic patients with the large immune deposits had a recent/concurrent acute bacterial infection, prompting a diagnosis of infection-associated glomerulonephritis and treatment with antibiotics. In the remaining three patients, no infection was identified and corticosteroids were initiated. Three of nine patients recovered kidney function (one recovered kidney function after liver transplant); three patients developed chronic kidney disease but remained off dialysis; two patients became dialysis-dependent and one patient developed sepsis and expired shortly after biopsy. Within the total cohort of 118 patients with cirrhosis, 67 others also showed IgA deposits, albeit small; and 42 patients had no IgA deposits. Conclusions These cases provide support to the theory that liver dysfunction may compromise clearance of circulating immune complexes, enabling deposition in the kidney. At least in a subset of cirrhotic patients, a superimposed bacterial infection may serve as a “second-hit” and lead to acute glomerulonephritis with exuberant immune complex deposits. Therefore, a trial of antibiotics is recommended and caution is advised before immunosuppressive treatment is offered. Unfortunately, most of these patients have advanced liver failure; therefore both diagnosis and management remain a challenge.

Renal biopsy is the gold standard method for determining the diagnosis, treatment, and prognosis in children with renal disease. This study aims to evaluate the histopathological features of pediatric renal biopsies obtained from the national nephrology registry in the last two decades. Data recorded in the Turkish Society of Nephrology Registry System (TSNRS) in 1991 as well as in between 2001 and 2010 were analyzed. A total of 3892 biopsies were recorded; with the least number in 1991 (total 103 biopsies from 17 centers) and the highest number in 2008 (total 654 biopsies from 23 centers). Glomerular diseases constituted the main group in the registry (62.64%), followed by systemic diseases (20.06%). Focal and segmental glomerulosclerosis (FSGS) and Henoch-Schonlein purpura (HSP) nephritis (IgA vasculitis) were the most common glomerular and systemic diseases, respectively. Overall prevalence of renal amyloidosis and membranous nephropathy (MN) was quite low (1.87% and 1.56%, respectively) in all periods. Compared to 1991, there was an increasing trend in the frequencies of certain disorders including hemolytic uremic syndrome (HUS), IgA nephropathy, and HSP nephritis; and there was a decrease in acute proliferative glomerulonephritis (GN) in 2008. As well as demonstrating the etiologies of renal diseases which can only be identified by renal biopsies, this study provides important information regarding the changing patterns of histopathological findings due to better management of pediatric renal diseases over the years in Turkey.

Background and objectives. The mesangial deposition of IgA is rarely described with proliferative glomerulonephritis associated with Staphylococcus infection. Recently, this association has been increasingly recognized possibly due to the increased rate of Staphylococcus infection. Design setting, participants and measurements. We report two cases of methicillin-sensitive Staphylococcus aureus bacteremia associated with acute proliferative glomerulonephritis with dominant mesangial deposit of IgA. We searched MEDLINE (1960–2009) for similar reports. We pooled individual patient data and reported descriptive statistics of all published cases. Results. Forty-six cases were included in the final analysis. The mean age of presentation was 59, with a male predominance (84%). Clinical presentation was notable for rapidly progressive glomerulonephritis with nephrotic-range proteinuria and normal complement levels in 52 and 72%, respectively. Methicillin-resistant S. aureus (68%) was the most common pathogen isolated with a latent period ranging from 1 to 16 weeks. Diffuse mesangial proliferation was commonly found with crescentic lesions noted in 35% of the cases. Antimicrobial treatment was associated with renal recovery in 58% of the cases. Need for renal replacement therapy was significantly associated with pre-existing diabetes, hypertension and interstitial fibrosis seen on kidney biopsy. Conclusions. IgA-dominant post-Staphylococcus glomerulonephritis is a rare clinical entity with certain unique clinical and morphologic features. It is difficult to differentiate from primary IgA nephropathy in cases where the infection is not apparent. An acute onset of rapidly progressive glomerulonephritis, with normal complement levels and deposition of mesangial IgA in an elderly patient should raise suspicion for this rare form of glomerulonephritis.

Ubiquitin C-terminal hydrolase-L1 (UCH-L1), an important member of de-ubiquitination enzyme families involved in the ubiquitin-proteasome pathway, is expressed mainly in neural and reproductive systems as well as in some tumours. Recently, expression of UCH-L1 has been discovered in parietal epithelial cells of Bowman's capsules and some tubular epithelia in the kidney. However, whether UCH-L1 is expressed in the capillary tufts of the glomeruli has not yet become clear. In this study, we used immunohistochemistry, double immunofluorescence labelling, immunoelectron microscopy in kidney biopsy tissues and western blot in cultured rat podocytes to investigate the expression of UCH-L1 and the regulation of this expression in podocytes. The results demonstrated that UCH-L1 was expressed in podocytes and its expression was significantly higher in acute proliferative glomerulonephritis (APGN), lupus nephritis (LN), membranous glomerulonephritis (MGN) and IgA nephropathy than that in focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), minor abnormality and normal kidney tissues (p 0.05). Further tests indicated that the percentage of PCNA-positive podocytes in LN, APGN and IgA nephropathy was significantly higher than that in MCD, FSGS and normal control (p < 0.05). These data show for the first time that podocytes do express UCH-L1 and that its expression can be increased in these immunocomplex-mediated nephrites. The immune injury is a main cause for stimulating podocytes to express UCH-L1. The expression of UCH-L1 may be associated with the regeneration of podocytes as a repair response to immunocomplex-mediated injury.

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03+/-2% versus 0.32+/-0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4+/-1.9 versus 1.52+/-0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89+/-0.8 versus 0.73+/-0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.

Objective: Post-infectious glomerulonephritis typically occurs 7-14 days after an infection. However, in several children we observed acute glomerulonephritis (AGN) to develop concurrently with pneumonia. The objective of the study was to delineate the clinical course and outcome of pneumonia-associated AGN. Study design The hospital database was searched from 1984 - 1999 for c+hildren admitted with both acute pneumonia and AGN, each diagnosis having been made within 72 hours of each other. Results: 11 boys, age 3.8-12.7 years, were identified. Ten children had lobar pneumonia and 1 had an interstitial infiltrate. All responded to antibiotic therapy with resolution of fever and respiratory symptoms. Only 1 child developed an empyema. The mean ± SD hospital stay was 5.9 ± 3.9 days. All patients had an abnormal urinalysis with hematuria (gross hematuria in 5), proteinuria and cellular casts. At presentation, 7 children had a serum creatinine > 1.0 mg/dl and creatinine clearance ≤ 80 ml/min/1.73 m 2 ; in all, serum creatinine returned to normal and the creatinine clearance was > 80 ml/ min/1.73 m 2 on follow-up. Nine of the 11 children had a low serum complement C3, 3 of whom also had low complement C4. Anti-streptolysin-O (ASO) titers were elevated in all 10 children tested. Six children developed hypertension and received anti-hypertensive medications. Only 1 child was severely oliguric requiring peritoneal dialysis for 4 days. He underwent a kidney biopsy. which showed acute proliferative glomerulonephritis without crescents. Neither a biopsy nor dialysis was performed in the other children. At follow-up, blood pressure, urinalysis and serum complements had normalized in the 9 children in whom follow-up was available. Conclusion: Children with pneumonia who are found to have abnormal urinalysis, hypertension, azotemia or oliguria should be evaluated for concomitant glomerulonephritis. In most children, pneumonia-associated AGN runs a benign course and has a good prognosis, however, in some short-term medical intervention may be necessary.

Introduction Acute proliferative glomerulonephritis (AGN) may follow streptococcal or non-streptococcal infections that include bacterial, viral, fungal and parasites. Dengue infection is a mosquito-borne viral disease causing acute febrile illness that may be complicated by dengue haemorrhagic fever and shock syndrome. Dengue associated AGN in humans, however, has not been reported. Case report A 36-year-old man presented with oedema and frothy urine for 3 days. He had proteinuria of nephrotic range with microscopic haematuria. Renal function was normal and investigations: ASOT, ANA, VDRL and hepatitis screen were non-reactive. Renal biopsy showed acute proliferative glomerulonephritis with hump-like fuchsinophilic deposits at the subepithelial location along the glomerular capillaries. There were associated IgG and C3 immune deposits. Three weeks prior to this presentation, he was admitted for dengue with positive serology NS-1, which he recovered uneventfully. Discussion The latent interval between the preceding infection and onset of renal symptoms of AGN can range from 1 to 6 weeks. AGN is immunologically mediated disease and requires development of antibodies after an infection. It has been hypothesised that dengue virus infection elicits an immune response to the viral antigens. Immune-complex deposition and proliferative lesions were demonstrated in glomeruli of experimental mouse models infected with dengue infection.

Hepatitis C virus-associated glomerulonephritis. Effect of α-interferon therapy. Hepatitis C virus (HCV) infection may present as a primaiy glomerular disease. We report 34 adult patients who presented with proteinuria and had circulating anti-HCV antibodies. Primary risk factors included a history of intravenous drug abuse (56%) or blood transfusion (18%). Patients presented with nephrotic syndrome (71%) or with non-nephrotic proteinuria (29%) and had membranoproliferative or acute proliferative glomerulonephritis on renal biopsy. Signs of clinical liver disease were infrequent (18%), though elevated liver function tests were common (66%) and liver biopsy in 16 of 18 patients showed chronic active hepatitis. Cryoglobulinemia was frequent (59%), but only 44% had extrarenal manifestations. In 100% of cases tested, HCV RNA could be found in the serum or cryoprecipitates. Fourteen patients received interferon alpha for 6 to 12 months with a significant reduction in proteinuria but no improvement in renal function. A good clinical response correlated with disappearance of HCV RNA from the serum during treatment; however, relapse of viremia and renal disease was common after completing therapy. Evidence for HCV infection should be sought in all patients with primary glomerular disease. The optimal treatment strategy, however, remains to be defined.

All classical antipsychotics, such as chlorpromazine and haloperidol, have potent dopamine receptor-blocking properties. This unit describes the rat anti-Thy-1.1 model of acute proliferative glomerulonephritis for the study of chronic renal insufficiency. A procedure is detailed for the induction of glomerulonephritis in rats as well as measurement of daily urinary excretion of protein, which is a convenient, primary screening tool. The unit also provides methods for assessment of glomerular filtration rate and effective renal plasma flow in anesthetized rats with anti-Thy-1.1-induced renal insufficiency.

Neutrophil gelatinase-associated lipocalin (NGAL), one of the most promising next-generation biomarkers in clinical nephrology, has received extensive attention. However, the basic role of its receptor (NGALR) remains unclear. Here, we have assessed the expression pattern of NGALR in injured glomeruli and explored the possible mechanism of the NGALR involvement in inflammation in human mesangial cells (HMC). The expression pattern of NGALR was detected by immunohistochemistry in biopsy samples of 93 glomerulonephritis patients and healthy controls, and the regulation of NGALR by the proinflammatory cytokines, TGF-β1, TNF-α and IL-1β in HMC was analyzed by real-time PCR and Western blotting. NGALR was found to be expressed in glomeruli. Its expression was significantly higher in acute proliferative glomerulonephritis and lupus nephritis than that in other types of glomerulonephritis or healthy kidney tissues. In in vitro experiments, both mRNA and protein levels of NGALR were dramatically induced by treatment of IL-1β, whereas TGF-β1 or TNF-α did not have the same effect. Furthermore, it was shown that the IL-1β-induced NGALR expression is mediated via the MAPK/ERK signaling pathway by using pharmacological inhibitors. Interestingly, the basal mRNA levels of NGAL detected in HMC, could be induced by IL-1β. However, NGAL protein could not be detected, even with IL-1β treatment. The ability of HMC to express NGAL protein was ascertained by exogenous administration of NGAL. In conclusion, the data show that NGALR is differentially expressed in human glomerular disease and is significantly up-regulated by Il-1β in HMC via MAPK/ERK activation. Furthermore, exogenous NGAL can be uptaken into HMC.

Background. Renal disease is a complication of heroin addiction. Using renal biopsies in Caucasian patients, we studied the types of nephropathy associated with heroin abuse. Methods. Nineteen renal biopsies were performed on heroin addicts between January 1993 and December 2001. The indications for renal biopsy included proteinuria with or without renal insufficiency. Results. All 19 patients had serological evidence of hepatitis C virus (HCV) infection, one had hepatitis B virus surface antigen and three were HIV positive. Thirteen patients (68.4%) were found to have membranoproliferative glomerulonephritis (MPGN), 12 with type I and one with type III. Of the remaining patients, two had chronic interstitial nephritis, two had acute proliferative glomerulonephritis, one had amyloidosis and one had granulomatous glomerulonephritis with interstitial nephritis. No apparent decline in the incidence of renal disease was observed. Conclusions. In this cohort of male Caucasian heroin addicts, HCV-associated MPGN was the most frequent pattern of nephropathy, showing that the nephropathy associated with heroin abuse in Caucasians is not of the focal and segmental glomerulosclerosis type, in contrast to previous reports on African-Americans. This aspect may have important implications for patient management and prognosis.

Acute nephritic syndrome is clinically characterized by hematuria, proteinuria, oliguria, and volume overload with or without azotemia and histologically be acute proliferative glomerulonephritis. Acute post streptococcal glomerulonephritis is the commonest cause in children. There is a preceding infection prior to this condition in majority. This is one of the comonest causes of renal edema in children. Early recognition, prompt and aggressive therapy and adequate follow-up are mandatory. Prognosis is usually good unless associated with severe renal failure and crescentic glomerulonephritis where the outcome is relatively poor unless treatment is early and adequate. Pathologically acute proliferative nephritis is with diffuse proliferative glomerulonephritis with or without crescents. Immunosuppressive therapy is not needed in simple acute proliferative glomerulonephritis but is essential in modifying the outcome of crescentic glomerulonephritis. Delayed resolution, severe renal failure at onset, progressive renal failure and associated systemic features like skin rashes, joint pains, hepatosplenomegaly and persistent fever are the indications for biopsy. Overall the prognosis in classical post streptococcal acute proliferative glomerulonephritis is good.

This unit describes the rat anti-Thy-1.1 model of acute proliferative glomerulonephritis for the study of chronic renal insufficiency. A procedure is detailed for the induction of glomerulonephritis in rats as well as measurement of daily urinary excretion of protein, which is a convenient, primary screening tool. The unit also provides methods for assessment of glomerular filtration rate and effective renal plasma flow in anesthetized rats with anti-Thy-1.1-induced renal insufficiency.

Thrombocytopenia in patients with acute systemic lupus erythematosus (SLE) frequently presents the clinician with considerable diagnostic and therapeutic difficulties. In this Grand Round, we present a 48-yr-old woman with a 7 yr history of lupus, who presented with acute proliferative glomerulonephritis and nephrotic syndrome, pneumonia, profound hypocomplementaemia and a severe microangiopathic haemolytic anaemia with associated thrombocytopenia. Her thrombocytopenia proved initially refractory to conventional immunosuppressive therapy, and corticosteroids, and resolved only with plasma exchange and repeated fresh frozen plasma infusions. Serological testing revealed high-titre antinuclear antibodies (ANA) and markedly raised antibodies to double-stranded (ds) DNA, but no significant elevation in anticardiolipin antibodies. Platelet-associated IgG and IgM and antibodies to the CD36 glycoprotein antigen, expressed on platelets and endothelium, were detected in the serum. We address some of the difficult diagnostic and management issues raised by this complex patient and the possible immunopathological links between antibodies to CD36, immune-mediated red cell destruction, thrombocytopenia and thrombotic microangiopathic haemolytic anaemia.

To date, sarcocystis has been considered an asymptomatic infection in humans. Even though cases with glomerulonephritis have been reported in animals with sarcocystis, there have been no reports of a similar occurrence in humans. We report a case of acute proliferative glomerulonephritis and leukocytoclastic vasculitis in a patient with sarcocystis infestation.

African swine fever is a viral haemorrhagic disease of pigs which has been used as a model for the study of viral haemorrhagic diseases in man. The acute course of the disease is characterized by acute proliferative glomerulonephritis, with viral replication in mesangial cells and occasional focal necrosis of the renal tubular system; hyperplasia of the collecting ducts is associated with evident virus replication. Haemorrhages have been attributed to endothelial dysfunction, aggravated by virus replication in endothelial cells in the final stages of the disease. The renal interstitium displays intense oedema and an infiltrate largely composed of macrophages. Virus replication has also been observed in fibroblasts and in the smooth-muscle cells of arterioles and venules. In subacute-chronic forms of the disease, various types of glomerulonephritis are observed, ranging from mesangial proliferative glomerulonephritis to focal and segmental hyalinosis associated with immune-mediated phenomena. No striking changes are reported in the renal tubular system. Interstitial haemorrhages are associated with diapedesis due to immunologically mediated events. The interstitium has also been found to contain a lymphohistiocytic infiltrate with abundant plasma cells. No evidence has been reported of viral replication in any cell population.

304 cases of glomerulonephritis were biopsied in Tunisia and studied morphologically. The incidence of glomerulonephritis with marked proliferation of endocapillary cells was 60%, a figure considerably higher than in other large series. Using a Clq binding assay, statistically significant levels of immune complexes were found in cases of acute proliferative glomerulonephritis. Amongst other types of glomerulonephritis, circulating immune complexes were frequently found in systemic lupus erythematosus but only in a low percentage of primary glomerulonephritis with or without immunoglobulin deposits.

Ultrastructural cytochemistry for nonspecific esterase (NSE) was performed on normal and nephritic rabbit kidneys. In normal glomeruli distinct reaction deposits appearing as electron-dense granules were present in visceral epithelial cells (podocytes) and epithelial cells of Bowman's capsule, but only a few small or minute deposits were seen in some endothelial and mesangial cells. In acute proliferative glomerulonephritis (Masugi nephritis), many reaction deposits occurred in mononuclear cells accumulating in glomerular tufts which presented the characteristic features of monocytic cells. Macrophages which had migrated into subendothelial space as well as epithelioid cells and multinucleated giant cells, all of which are known to be derived from monocytes, also exhibited the reaction product. The NSE granules in mesangial and endothelial cells were much smaller and fewer in number than those in monocytic cells. The present method may contribute to the more precise differentiation of monocytic cells from mesangial and endothelial cells in proliferative glomerulonephritis.

Summary A 26-year-old patient with no previous history of renal disease developed acute non-streptococcal crescentic glomerulonephritis with severe renal failure in the 17th week of her second pregnancy. It became necessary to treat her with haemodialysis to maintain the blood urea around 25 mmol/l. The haemoglobin was maintained above 9 g/dl with regular blood transfusions and the blood pressure was controlled with hypotensive drugs. Measurement of fetal biparietal diameter and human placental lactogen indicated normal fetal growth and placental function. The patient spontaneously delivered a healthy infant at 32 weeks. Haemodialysis requirements decreased post partum and the patient even managed without dialysis for 12 weeks. Renal function, however, remained severely impaired and maintenance haemodialysis was again necessary a t nine months post partum. Glomerulonephritis complicating pregnancy is reviewed and the management of acute and chronic renal failure in pregnancy is discussed.

A 5-year-old boy had transient glomerulonephritis following measles infection. Serologic studies at the early onset of the disease showed decrease of serum C3, C4, and Clq levels with normal serum properdin factor B. Renal glomerular histology revealed a mild acute proliferative glomerulonephritis. Measles virus antigen, C3, C4, and immunoglobulin G (IgG) were demonstrated in the glomerulus, suggesting an immune complex deposition. Ultrastructurally, subepithelial, intramembranous, and subendothelial electron-dense deposits were noted, suggesting a postinfectious immune complex glomerulonephritis. It is suggested that the measles virus antibody complexes are deposited in the glomerulus and activate the classic pathway of complement, leading to a self-limited glomerulonephritis.

Twenty-five renal biopsies from patients with Henoch--Schönlein nephritis were examined using light microscopy, immunofluorescence, 1 micrometer plastic-embedded sections and electron microscopy. The 1 micrometer plastic-embedded sections and electron microscopy showed deposits in mesangial, subendothelial and subepithelial sites. Some of the latter were very large and similar to those which have been described as "humps" in acute proliferative glomerulonephritis. Immunofluorescence showed the mesangial deposition of IgG, IgA and C3 with extension into a peripheral position in some cases. Fibrin was frequently found associated with crescents. The case for Henoch--Schönlein disease being mediated, in part at least, by immune complex deposition, is presented.

In 16 of 52 cases (32.5 per cent) of glomerulonephritis associated with glomerular subendothelial electron dense deposits, we detected endothelial endocytosis of osmiophilic material. Twelve patients had systemic lupus erythematosus, two had poststreptococcal glomerulonephritis, and two had idiopathic immune complex glomerulonephritis. The endocytosis was not observed in 13 patients suffering from membranoproliferative glomerulonephritis, in seven suffering from focal sclerosing glomerulonephritis, and in one suffering from hereditary nephritis. Therefore, the potential for endocytosis appeared to vary according to the illness. By light microscopy the 16 specimens exhibited features of acute proliferative glomerulonephritis. All the 14 with tissue sufficient for immunofluorescence study displayed deposition of immunoglobulins and complement along capillary loops and within the mesangium. By electron microscopy many of the subendothelial deposits were unassociated with endocytosis of osmiophilic matter, yet when endocytosis occurred, it was prominent. Hypertrophied endothelial cells occurred in zones of endocytosis. In nine of 16 cases small vacuoles within endothelial cells contained material of an electron density comparable to that of intramembranous and subendothelial deposits, but lyosomal degradation of the material was not noticed. There was frequent direct communication between osmiophilic material in capillary lumens, the subendothelial aspect of the glomerular basement membrane, and endothelial cytoplasmic processes. These communications suggested movement of osmiophilic material in some fashion. Neutrophils featuring vacuoles that contained osmiophilic material were only rarely observed, indicating that they may not assume a major role in degradation of deposits. Phagocytic activity of mesangial cells and nonresident monocytes was not studied. On the basis of our findings we propose that endothelial endocytosis of osmiophilic material might constitute a component of a transport mechanism or a digestive mechanism of glomerular immune deposits located in the subendothelial region.

Although a diminished fractional excretion of sodium (FENa) is the hallmark of acute proliferative glomerulonephritis (APGN), an enhanced natriuresis per glomerular filtration rate (GFR) in the chronic phases of this disease has been reported. We studied this adaptive response utilizing two different split-bladder dog models with unilateral, and a third group of dogs with bilateral Masugi's nephritis. Group I. Six dogs with unilateral nonaccelerated APGN studied a mean of 6 days after induction had a mean base-line APGN/intact kidney GFR of 31/50 ml/min (P less than 0.005) and FENa of 0.2/0.75% (P less than 0.005). Acute volume expansion caused a smaller absolute increase in FENa from the APGN kidney, 1.6%, than from the intact kidney, 4.0%, (P less than 0.01). Maximum tubular secretion of rho-aminohippuric acid/GFR (TmPAH/GFR) measured in three dogs was higher in the APGN kidney than intact kidney, 13.1 vs. 9.3 mg/dl. Subsequent studies on three of the six dogs when the disease had become chronic demonstrated a reversal in the pattern of sodium excretion in response to volume expansion. Group II. Six dogs with accelerated unilateral APGN (dogs presensitized to antibody source) studied a mean of 5 days after induction had a mean base-line APGN/intact kidney GFR of 16/57 ml/min and FENa of 0.22/0.12% (P less than 0.1). Contrary to group I, volume expansion caused a greater absolute increase in FENa from the APGN kidney, 5.8%, than from the intact kidney, 2.9% (P less than 0.05). TmPAH/GFR studied in four dogs was similar for both kidneys, 17.9 and 18.5 mg/dl for the APGN kidney and intact kidney, respectively. Group III. Sequential studies were performed on seven dogs with bilateral nonaccelerated APGN. Initially each demonstrated sodium retention and a smaller absolute increase in FENa in response to volume expansion compared to a predisease control study. With disease progression, volume expansion induced a greater absolute increase in FENa than in the control study. We concluded that (a) the fractional excretion of sodium from the APGN kidney will be less or greater than the contralateral intact kidney or control study depending on the severity and/or chronicity of the disease, possibly as the result of morphologic alterations; (b) the degree of extracellular fluid volume expansion is an important variable influencing similarity of glomerulotubular balance between the APGN and contralateral intact kidney; and (c) the "intact nephron hypothesis" applies in a limited fashion to kidneys with APGN in the absence of volume expansion just as it does for kidneys with chronic glomerulonephritis or pyelonephritis.

Kidney biopsies from 23 bitches with pyometra and an entire kidney from four pyometra bitches were examined by light microscopy. Kidney tissue was also taken from three bitches at different intervals after ovariohysterectomy for pyometra. All the pyometra bitches had membranous glomerulonephritis or mixed proliferative and membranous glomerulonephritis. Two of the bitches had intraglomerular hyaline nodules resembling those seen in conjunction with diabetes in human beings. The degree of glomerular damage could be correlated with the reduction in glomerular filtration rate determined by function tests. The proximal tubules generally contained numerous hyaline droplets but the degree of this change could not be correlated to the degree of glomerular damage. A yellow pigment, a lipofuscin, was regularly present in the proximal tubules as well as epithelial proliferation and mitoses. Focal atrophy of tubules also occurred, presumably because of obliteration of glomeruli. The cortical interstitium contained collections of mature and immature plasma cells, often surrounding the glomeruli. When the kidneys from three bitches were examined after ovariohysterectomy for pyometra, the glomerular damage in two had regressed to leave only slight thickening of the capillary walls. In the third bitch, examined only 14 days after ovariohysterectomy, healing was partial. Kidney tissue from five bitches was also examined by electron microscopy. The glomerular endothelial cells were swollen and the basement membrane was grealy thickened. With more severe degrees of glomerular damage, an electron-dense material was deposited along the inner surface of the basement membrane and the swollen mesangial cells contained numerous inclusions. There was focal fusion of the foot processes of the glomerular epithelial cells; in one bitch with heavy proteinuria, the fusion was widespread. The proximal tubules contained numerous protein absorption droplets representing resorbed protein. The tubular basement membrane at all levels was thickened. Because of similarities with some other types of renal damage (nephrotoxic nephritis in dogs and acute proliferative glomerulonephritis in human beings), the possibility is broached that the renal lesion in pyometra is the result of an immunobiological process.

The relationship between the immunofluorescent findings and the light microscopic findings in 433 adult patients suffering from primary glomerulonephritis is discussed. Diffuse deposition of immunoglobulin G (IgG) in a granular pattern along the glomerular basement membrane appears characteristic of membranous glomerulonephritis. Scattered deposits of β 1 C-globulin and IgG are found in acute proliferative glomerulonephritis. In focal glomerulonephritis the presence of diffuse mesangial immunoglobulin A (IgA) is one of the most frequent lesions encountered demonstrating a new clinicopathologic entity. In rapidly progressive glomerulonephritis with epithelial crescents, deposition of fibrinogeh is the most conspicuous immunofluorescent abnormality; the deposition of IgG in a linear smooth pattern is rare. In many instances, when the light microscopic findings are difficult to interpret, Immunofluorescence may reveal a pattern which is commonly associated with a characteristic abnormality on light microscopy.

1. Platelet survival was measured in patients with acute proliferative glomerulonephritis or chronic renal failure and also in control subjects. 2. Platelet survival is markedly reduced in acute proliferative glomerulonephritis as compared with control subjects; it was slightly reduced in patients in chronic renal failure due to interstitial renal disease and maintained on dialysis.

Necrotizing myositis and acute proliferative glomerulonephritis is described in a patient with Behcet's syndrome. Both of these rare manifestations resolved spontaneously while the underlying disease remains active.

Experimental immune complex glomerulonephritis induced with bovine serum albumin (BSA) or sheep serum (SS) was studied under immunofluorescent, light and electron microscope. Immunofluorescent study revealed fine and coarse granular immunofluorescent deposits along the glomerular basement membrane (GBM). Electron microscopic examination showed humps of electron-dense deposits in the spaces between the processes of the podocyte external to the GBM. Light microscopic examination showed acute proliferative glomerulonephritis. Taking human immune complex glomerulonephritis into account, the results of the present Study are of considerable significance to the further study of etiology, pathogenesis, pathological changes, clinical manifestations, prevention and treatment of glomerulonephritis. In addition, similar results were obtained by using either BSA or SS. Under ordinary conditions, it is suitable to use SS instead of BSA, because the former is easy to get and cheaper.

THE OBSERVATION 1 has been made that dogs with large arteriovenous fistula loads "spontaneously" acquired endocarditis and that in some acute proliferative glomerulonephritis also developed in the period of six weeks to five months following the construction of their arteriovenous shunts. The mechanism of these observations would appear to depend on the fact that the application of a systemic cardiovascular stress, such as large arteriovenous fistulas, causes certain physiological alterations to occur within the dogs, which result in a significant and specific increase in the susceptibility of the endothelial surfaces of the heart and kidneys to bacteria or to the products of bacterial infection. This increase in susceptibility is so great that the animals can acquire their endocarditis from the relatively few microorganisms which gain entrance into their blood streams by adventitious routes. This fortuitous entrance of bacteria through skin or intestinal mucosal abrasions into the blood stream no doubt

Transient glomerular hypercellularity in poststreptococcal glomerulonephritis was analysed by electron microscopy. Large numbers of monocytes as well as polymorphonuclear leukocytes were observed not only in the capillary lumen but also in the mesangial area. The result suggests that the disappearance of phagocytes from the glomeruli is one of the best histological explanations for the resolution of acute proliferative glomerulonephritis.

Currently, immunological mechanisms are responsible for 70% of cases of glomerulonephritis. Immunofluorescent staining of tissue obtained by renal biopsy has been the major factor in recognition of immunological mechanisms in human renal disease, but electron microscopy and serological studies have also contributed. The first immunopathological mechanism of renal disease to be demonstrated experimentally was glomerulonephritis due to anti-basement membrane antibody. This antibody is recognized by the distinctive linear pattern of glomerular staining by immunofluorescence. Similar staining is present in kidneys of patients with Goodpasture's syndrome and in a few cases of crescentic nephritis without lung lesions. Antibody is also present in the circulation in these patients and can be demonstrated consistently by a recently developed radio-immunoassay. The second principal immunopathological mechanism in glomerulonephritis, is deposition of immune complexes. One of the principal factors governing glomerular deposition of these complexes is their size which depends on the proportion of antigen to antibody. The most potent complexes are small and soluble and are usually formed in states of slight antigen excess. Immune complexes are responsible for most cases of human glomerulonephritis; their presence within glomeruli can be recognized with immunofluorescence by a granular pattern with antisera against immunoglobulin and complement. In a membranous nephropathy deposits are small and distributed uniformly along glomerular capillary walls but in acute proliferative glomerulonephritis deposits are larger and have a less uniform distribution. Immunological studies of human renal disease have recently revealed mechanisms which have not yet been reproduced experimentally. One of these being mesangial 1gA disease, a disorder named after the most characteristic feature demonstrated by immunofluorescence. Secondly, in one form of membrano-proliferative glomerulonephritis both glomerular and tubular lesions may be due to activation of complement through the alternative pathway without involvement of antibody. These studies show that immunological investigations in patients with renal disease are not only valuable for diagnosis and prognosis in the individual case, but also contribute to fundamental knowledge about pathological mechanisms of tissue damage.

Acute intrinsic renal failure occurred in an adult patient with Escherichia coli septicemia. The clinical course did not include any of the circumstances usually present when acute renal failure complicates Gram-negative sepsis. A renal biopsy showed acute proliferative glomerulonephritis. There was no evidence to support other known causes of acute parenchymal renal failure, such as poststreptococcal glomerulonephritis, subacute bacterial endocarditis, or vasculitis. The patient recovered completely with antibiotic therapy, and renal function returned to normal within two weeks. An immunologic mechanism involving E coli was considered responsible for the acute renal failure. ( JAMA 238:1389-1390, 1977)