Acute presentation and persistent glomerulonephritis following streptococcal infection in a patient with heterozygous complement factor H-related protein 5 deficiency

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.     

Proteinuria following transplantation. Correlation with histopathology and outcome

A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. Twenty-one patients had received kidneys from living-related donors, the remaining 56 from cadaveric donors. The cause of proteinuria in these 77 patients was as follows: transplant glomerulopathy (30), allograft glomerulonephritis (22), chronic rejection (21), renal vein thrombosis (2), diabetic glomerulosclerosis (1), and hypertensive nephrosclerosis (1). Of the 22 patients who developed glomerulonephritis in the transplanted kidney, 6 had recurrent disease (3--membranous glomerulopathy, 2--focal sclerosis and hyalinosis, 1--membranoproliferative glomerulonephritis); 6 developed de novo glomerulonephritis; and in 10 the type of glomerulonephritis could not be classified as recurrent or as de novo because of lack of characterization of the original kidney disease. Renal vein thrombosis occurred in association with other lesions in an additional 5 cases (3--chronic rejection; 2--membranous glomerulopathy). In follow-up only 23.4% (18 of 77) of the patients maintained prolonged graft function; the majority of grafts being lost within one year of the development of persistent, heavy proteinuria. Of the 18 patients who retained their grafts, 8 had glomerulonephritis, 5 transplant glomerulopathy, and 5 chronic rejection. This study confirms the poor prognosis that has been reported with the development of nephrotic-range proteinuria in renal allograft recipients.     

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.     

Thin basement membrane nephropathy associated with other glomerular diseases

Many reports confirm that thin basement membrane nephropathy (TBMN) commonly occurs together with other glomerular diseases such as minimal change glomerulonephritis, diabetes, membranous nephropathy, immunoglobulin (Ig)A glomerulonephritis, and focal segmental glomerulosclerosis. We postulate 3 explanations for these observations. The association of minimal change glomerulonephritis with TBMN probably is artifactual whereas the association with diabetes and membranous glomerulonephritis probably is coincidental. However, the link between TBMN and IgA disease and focal segmental glomerulosclerosis may be pathogenetic. Clinical evidence indicates that the presence of an associated glomerulopathy significantly worsens the prognosis of TBMN. Thus, patients with TBMN and another glomerular lesion usually have more marked proteinuria, and are more likely to have hypertension and renal insufficiency. The frequency of another glomerulopathy in patients with TBMN means that all patients in whom TBMN is suspected but who have heavy proteinuria or renal insufficiency should undergo a renal biopsy examination. However, there is no evidence that TBMN alters the prognosis of another glomerulopathy, and, in particular, patients with TBMN and IgA disease do not have different clinical features or a worse prognosis than those with IgA disease alone.     

Membranous glomerulonephritis in a patient with ankylosing spondylitis: a rare association

Ankylosing spondylitis is a chronic inflammatory disease of the vertebral joints and soft tissues. Renal involvement, apart from amyloidosis, is rare in this disorder. Of the various glomerulonephritides reported in association with ankylosing spondylitis, IgA nephropathy is the most common. Membranous glomerulonephritis occurs very rarely in patients with ankylosing spondylitis, and only four such cases have been reported in the available English literature. Due to the rarity of this association, membranous glomerulonephritis may not initially be considered in patients with ankylosing spondylitis and proteinuria. We report the case of a 29-year-old man with ankylosing spondylitis who presented with pedal edema and was detected to have nephrotic syndrome. A percutaneous renal biopsy showed features of membranous glomerulonephritis with capillary wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found on extensive investigations. Membranous glomerulonephritis is extremely rare in association with ankylosing spondylitis, the present case being the fifth such report. The exact relationship of these two entities (etiological or coincidental) still needs to be elucidated. The occurrence of this rare association needs to be recognized and differentiated from other more common causes of renal involvement in ankylosing spondylitis.     

Effect of combination therapy (ribavirin and interferon) in HCV-related glomerulopathy.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis throughout the world. Several extrahepatic manifestations, including glomerulonephritis, have been reported to be associated with this type of infection. Cryoglobulinaemic and non-cryoglobulinaemic membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) are the commonest lesions associated with HCV. Results of treatment of these patients with interferon therapy have been disappointing, since relapse of the viraemia and subsequent relapse of the renal disease are major problems. Combination of interferon with ribavirin in patients with chronic liver disease has been shown to increase the rate of sustained response. METHODS: In this work, 20 patients with HCV-associated glomerulopathy were subjected to an in-depth evaluation of their kidney lesions and HCV involvement. Laboratory, histopathological, immunohistochemical, and electron-microscopy techniques were used. The patients received interferon therapy for 12 months; in interferon-resistant subjects, interferon was combined with ribavirin. RESULTS: MPGN was the commonest kidney lesion, being reported in 85% of these cases, followed by MN and mesangioproliferative glomerulonephritis (10 and 5% respectively). Mixed cryoglobulinaemia was encountered in 60% of the cases. Twelve months' anti-viral treatment resulted in aviraemia in 25% of cases, while liver enzymes were normalized in 75%, 24-h proteinuria significantly decreased (from median 4 g to 1.10 g, P=0.001), serum albumin increased (from median 2.50 to 3.55 g/dl, P=0.012), lower viral titres (from median 1.15 to 0.53 mega-Eq/ml, P=0.049), and C3 and C4 concentrations returned to normal. Basal serum creatinine and viral titres were important determinants of response to treatment. CONCLUSION: This study supports the relationship between HCV and glomerulonephritis, especially MPGN, and the use of a combination of interferon and ribavirin in the treatment of selected cases of HCV-related glomerulopathy.     

Focal segmental glomerulosclerosis in a 32-year-old kidney allograft after 7 years without immunosuppression.

In kidney allografts, focal segmental glomerulosclerosis (FSGS) has been described as recurrent, de novo, or a histological variant of chronic transplant glomerulopathy. We describe a unique case of de novo FSGS in a renal transplant not accompanied by any feature of rejection in a patient who had not been immunosuppressed for several years. A 58-year-old woman received a histoidentical living-related kidney transplant for end-stage renal disease due to chronic pyelonephritis. Twenty-four years after the transplant she voluntarily discontinued all immunosuppressive medication. Seven years later she presented with nephrotic syndrome, mild renal failure, and positive serology for hepatitis C virus (HCV) antibody. The kidney transplant biopsy disclosed de novo FSGS. Features of acute or chronic rejection, including chronic transplant glomerulopathy, were not seen. The pathogenesis of this lesion is probably related to sustained and prolonged glomerular hyperfiltration; alternatively, HCV infection may have triggered or accelerated the appearance of FSGS.     

Renal biopsy appearances in rheumatoid disease

The renal biopsies of 30 patients with rheumatoid arthritis and clinical evidence of renal disease were reviewed; only patients in whom the intravenous pyelogram was normal were subjected to biopsy, thus excluding those with papillary necrosis and chronic pyelonephritis. Tissue was studied by light, electron and immunofluorescence microscopy. There were 13 cases of mesangial change, 9 of membranous glomerulonephritis, 4 of tubulointerstitial change, 2 cases of focal segmental glomerulosclerosis, 1 case of amyloid and 1 of diffuse proliferative glomerulonephritis with crescents. All 9 patients with membranous glomerulonephritis but only 6 of 13 with mesangial change had received gold or penicillamine. We found no evidence of "glomerulitis" or of a rheumatoid vasculitis.     

Membranoproliferative glomerulonephritis associated with a mixed-cell germinal ovary tumor

We describe a patient with membranoproliferative glomerulopathy associated with a mixed-cell germinal ovary tumor (embryonal and dysgerminoma components). Advanced renal failure ensued without remission of nephrotic syndrome after surgery. Five other cases of ovary tumor associated with glomerulopathy and reported in the literature are reviewed. The association between membranoproliferative glomerulonephritis and mixed-cell germinal ovary tumor has not been previously reported.     

Proliferative glomerulonephritis associated with reflex nephropathy.

A case of unilateral reflux nephropathy treated by initial ureteral reimplantation and subsequent nephrectomy is reported. Pathologic examination of the resected kidney showed unsuspected proliferative glomerulonephritis. The relationship of chronic atrophic pyelonephritis, as seen in reflux nephropathy, and glomerulonephritis is discussed to emphasize that reflux nephropathy does not exclude the presence of other renal disease that may complicate the long-term care of the patient.     

Hepatitis B virus associated focal and segmental glomerular sclerosis: report of two cases and review of literature

The hepatitis B virus (HBV) is estimated to have infected about 350 million people worldwide, making it one of the most common human pathogens. Renal involvement is among its most common extra hepatic manifestations and usually manifests in the form of immune complex mediated glomerulopathy, such as membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN), mesangioproliferative glomerulonephritis and immunoglobulin A (IgA) nephropathy. Occurrence of focal and segmental glomerular sclerosis (FSGS) with HBV infection is rare and only five cases have been reported earlier. We report two cases of hepatitis B associated FSGS. In both the cases, HBsAg was demonstrated in the renal tissue and both the cases showed response to treatment with lamivudine, thus indicating a possible causal association between the viral infection and occurrence of nephrotic syndrome.     

Hepatitis B virus-associated glomerulonephritis: electron microscopic studies in 98 children

Ninety-eight children with glomerulonephritis concomitant with hepatitis B surface HBs antigenemia were studied, the antigenemia being first documented at the clinical onset of glomerulopathy. Initial diagnoses, based on examination of the paraffin sections, varied, membrano-proliferative, mesangial, and membranous glomerulonephritis being most frequently considered. However, electron microscopic examination showed that 77 children had a uniform type of glomerulopathy, irrespective of the light microscopic appearance. This type was diagnosed as secondary membranous glomerulonephritis. The clinical course of this nephropathy was relatively indolent and short. Moreover, in many children, elimination of some hepatitis B virus (HBV) antigens from the circulation was also associated with clinical remission of glomerulopathy. The remaining 21 children with HBs antigenemia had various morphological forms of glomerulonephritis, these being similar to their idiopathic counterparts in both morphology and clinical course. The distinct clinical and morphological picture of secondary membranous glomerulonephritis with HBs antigenemia occurring in 77 of 98 children supports the hypothesis that HBsV-associated glomerulonephritis is of the secondary membranous type. Thus, we conclude that in children HBV antigenemia associated with glomerulonephritis other than secondary membranous is coincidental.     

Epidemiology of chronic renal diseases

Autopsies of all uraemic patients in Leningrad for three years, and materials of the City Nephrological Service have demonstrated that the structures of nephrological diseases in their early and terminal stages were different. Chronic glomerulonephritis has been noted in patients with normal renal function just as often as chronic pyelonephritis but the former prevails considerably among the causes of uraemia. The proportion of polycystic kidney disease, amyloidosis, and diabetic nephropathy increases in patients with chronic renal failure. Due to these changes and the difference in the death age of patients with various diseases the majority of patients suitable for treatment with long-term dialysis suffer from chronic glomerulonephritis and only 14.89–20.5% from chronic pyelonephritis.     

Xanthogranulomatous pyelonephritis in children

Xanthogranulomatous pyelonephritis usually occurs in women 50 to 60 years old, and has the distinct clinical presentation suggestive of a renal mass. Since 1963 an increasing number of children with xanthogranulomatous pyelonephritis have been reported in the literature, with data suggesting that the characteristics of the disease are different from those in adults. We compared our children with xanthogranulomatous pyelonephritis to adults who had been described in the literature and to our cases of chronic pyelonephritis to determine whether xanthogranulomatous pyelonephritis in children is an entity as clearly different from chronic pyelonephritis as it is in adults. Twenty-one cases were eliminated from the study because of incomplete charts. We found 39 cases in which nephrectomy had been done for an anatomical diagnosis of chronic or xanthogranulomatous (8) pyelonephritis. Average age at presentation, duration of clinical course and sex distribution were similar in both groups. The left kidney was involved more often in both groups. Severe malnutrition, urolithiasis, reno-cutaneous fistula and negative urine cultures were more frequent in cases of xanthogranulomatous pyelonephritis, while obstructive nonlithiasic uropathy occurred more often in cases of chronic pyelonephritis. Microorganisms were similar in both groups and Escherichia coli was isolated most frequently. All cases of xanthogranulomatous pyelonephritis were of the diffuse type with areas corresponding to all histological stages. Our study suggests that perhaps in children xanthogranulomatous pyelonephritis occurs the same as chronic pyelonephritis, and is determined possibly by an affected immune response secondary to malnutrition and by the presence of urolithiasis.     

Immunotactoid (microtubular) glomerulopathy: an entity distinct from fibrillary glomerulonephritis?

Immunotactoid glomerulopathy (IT), or alternatively, microtubular glomerulopathy, is a term that has been used by some investigators to encompass those glomerulopathies characterized by the presence of fibrillar or microtubular deposits which are distinguished from amyloid principally by their larger size and lack of reactivity with the Congo red reagent. A case is presented here of IT as it was initially described. The present case, and a review of the literature, suggest that the diagnosis of IT be restricted to those glomerulopathies associated with large, at times organized, microtubular deposits. Terms such as fibrillary glomerulonephritis, or alternatively Congo red-negative amyloidosis-like glomerulopathy, could then be used to describe those patients with smaller, fibrillar glomerular deposits having an appearance closely resembling amyloid. We believe it is possible to separate the entities fibrillary glomerulonephritis and IT on morphological grounds. This is a potentially useful distinction that identifies patients who are likely to have or develop clinical evidence of a lymphoplasmacytic disorder or dysproteinemia, which are associated with deposits of IT, and distinguishes them from patients with fibrillary glomerulonephritis, of whom only a single case has been linked to such clinical findings.     

Renal infections and pyelonephritis as the main cause of renal failure and the associated glomerulopathy

In a retrospective study of 113 patients with chronic renal failure, including 39 dialysis patients, evidence of urinary infection and pyelonephritis was found in 72% of cases. Even in the majority of the cases diagnosed by renal biopsy as chronic glomerulonephritis, the clinical and laboratory data pointed clearly to the presence of pyelonephritis. Traditionally, the pyelonephritis in such cases is considered to be secondary to an already present chronic glomerulonephritis of unknown aetiology, or following a subclinical or forgotten acute poststreptococcal glomerulonephritis. However, the relationship of chronic glomerulonephritis to streptococcal tonsillitis is doubtful, and scientifically not proved either by serological, epidemiological or other studies. Classical acute poststreptococcal glomerulonephritis is relatively rare, while urinary infections and pyelonephritis in children are extremely common. Many of the incompletely cured cases of pyelonephritis in childhood could proceed to chronicity with progressive destruction of the renal parenchyma, and present later in adult life as chronic renal failure. Ample evidence is cited, pointing to the possibility that most of the glomerulopathies considered by several authors to be the main cause of renal failure could have been produced by the renal parenchymal infection. In order to diminish the mortality from renal failure, and the need for dialysis and transplantation, efforts should be directed to the early detection and control of urinary infection in children and in selected populations.     

Nephrotic syndrome secondary to chronic pyelonephritis and ureterovesical reflux.

Vesicoureteral reflux and chronic pyelonephritis are usually associated with proteinuria of less than 1 gm. per 24 hours. When there is massive proteinuria an associated glomerulopathy is usually present. We describe a patient who had nephrotic syndrome with radiological evidence of ureterovesical reflux and histological evidence of chronic pyelonephritis without associated glomerulonephritis.     

Use of radioimmunoassay for the detection of circulating antistreptococcal antibody in patients with glomerulonephritis

A method of radioimmunologic quantitation of antibodies to streptococcal antigen separated from the cell wall extract of group A type T₁₂ strain has been developed. The highest values of radioactive antigen binding were observed in acute glomerulonephritis (75%), as compared to chronic glomerulonephritis in which values of 25% to 56% were found depending on the morphology of renal changes. It was shown that none of the patients with pyelonephritis, Alport's syndrome, lupoid nephritis and polycystic renal disease had elevated antistreptococcal antibody levels. In contrast to this, all patients with tonsillitis and proteinuria exhibited increased titre of this antibody.It was shown that the antigen is related neither to M-protein nor to group A polysaccharide and that it is not type-specific because the binding of antigen T₁₂ may be inhibited by the antigen produced from strain T₅. Although the antigen is not type-specific, some differences in the response to antigens prepared from various types of streptococci in patients with different form of chronic glomerulonephritis are observed.     

Pattern of double glomerulopathy in children

Occasional case reports have been issued on children with double glomerulopathy, involving either the coexistence of two different glomerulopathies or superimposition of a second glomerulopathy onto a first. A retrospective clinicopathological review of 294 children who had received renal biopsies resulted in 9 (3.1%) being confirmed to have double glomerulopathy. Superimposed glomerulopathy was diagnosed by a second renal biopsy in two cases, and coexistence of two glomerulopathies was confirmed by single biopsy in seven. Original glomerulopathies were those with a chronic course, such as Alport syndrome, IgA nephropathy, relapsing minimal-change nephrotic syndrome, Frasier syndrome, and thin basement membrane nephropathy. The superimposing glomerulopathies were common types in children, such as postinfectious glomerulonephritis, IgA nephropathy, and Henoch-Schönlein nephritis. Thus, the pattern of double glomerulopathy was considered to be due to the chance occurrence of two different glomerulopathies without a common pathogenesis. Acute nephritic symptoms of superimposed glomerulopathies resolved almost completely during follow-up in most cases. Double glomerulopathies are not rare in children and may occur by chance alone in most cases. The possibility of superimposed glomerulopathy should be suspected if the clinical course of a glomerulopathy changes atypically. However, the long-term influence of a superimposed glomerulopathy on renal functional deterioration remains unclear.