M. Barry Stokes

Acute Phosphate Nephropathy following Oral Sodium Phosphate Bowel Purgative: An Underrecognized Cause of Chronic Renal Failure

The findings of diffuse tubular injury with abundant tubular calcium phosphate deposits on renal biopsy are referred to as nephrocalcinosis, a condition typically associated with hypercalcemia. During the period from 2000 to 2004, 31 cases of nephrocalcinosis were identified among the 7349 native renal biopsies processed at Columbia University. Among the 31 patients, 21 presented with acute renal failure (ARF), were normocalcemic, and had a history of recent colonoscopy preceded by bowel cleansing with oral sodium phosphate solution (OSPS) or Visicol. Because the precipitant was OSPS rather than hypercalcemia, these cases are best termed acute phosphate nephropathy. The cohort of 21 patients with APhN was predominantly female (81.0%) and white (81.0%), with a mean age of 64.0 yr. Sixteen of the 21 patients had a history of hypertension, 14 (87.5%) of whom were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The mean baseline serum creatinine was 1.0 mg/dl, available within 4 mo of colonoscopy in 19 (90.5%) patients. Patients presented with ARF and a mean creatinine of 3.9 mg/dl at a median of 1 mo after colonoscopy. In a few patients, ARF was discovered within 3 d of colonoscopy, at which time hyperphosphatemia was documented. Patients had minimal proteinuria, normocalcemia, and bland urinary sediment. At follow-up (mean 16.7 mo), four patients had gone on to require permanent hemodialysis. The remaining 17 patients all have developed chronic renal insufficiency (mean serum creatinine, 2.4 mg/dl). Acute phosphate nephropathy is an underrecognized cause of acute and chronic renal failure. Potential etiologic factors include inadequate hydration (while receiving OSPS), increased patient age, a history of hypertension, and concurrent use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

Pathology after Eculizumab in Dense Deposit Disease and C3 GN

Eculizumab might benefit C3 glomerulopathies mediated by dysregulation of the alternative complement pathway. Here, we report renal biopsy findings before and after eculizumab therapy in three patients with dense deposit disease and two with C3 GN. All pretreatment biopsies had glomerular and tubular basement membrane deposits that stained exclusively for C3 without significant Ig. After 1 year of therapy, there was reduction in active glomerular proliferation and neutrophil infiltration in three of five patients, consistent with effective C5 blockade, which prevents production of chemotactin C5a. One individual with mild mesangial disease had no significant change in activity or chronicity. One patient exhibited persistent activity and worsening chronicity despite therapy. Immunofluorescence showed no significant reduction in C3 or C5b-9, and electron microscopy revealed persistent deposits in all cases, suggesting a long t(1/2) of C5b-9 in extracellular matrix. Normal renal biopsies stained positive for C5b-9 in glomeruli, tubular basement membranes, and vessel walls, albeit at lower intensity than in C3 glomerulopathy. This indication of physiologic levels of C5b-9 activation in normal kidney potentially explains the localization of deposits in patients with dysregulation of the alternative complement pathway. All post-treatment biopsies showed de novo monoclonal staining for IgG-κ in the same distribution as C3 and C5b-9, mimicking monoclonal Ig deposition disease (MIDD). Staining of the γ heavy chain was restricted to the IgG2 and IgG4 subclasses, suggesting the binding of monoclonal eculizumab to C5 in renal tissues. The long-term effects of this apparent drug-tissue interaction are unknown.

Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

BACKGROUND AND OBJECTIVES Treatment with IFN is rarely associated with nephrotic syndrome and renal biopsy findings of minimal-change disease or FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We report 11 cases of collapsing FSGS that developed during treatment with IFN and improved after discontinuation of therapy. RESULTS The cohort consists of seven women and four men with a mean age of 48.2 yr. Ten of the 11 patients were black. Six patients were receiving IFN-alpha for hepatitis C virus infection (n = 5) or malignant melanoma (n = 1), three were receiving IFN-beta for multiple sclerosis, and two were treated with IFN-gamma for idiopathic pulmonary fibrosis. After a median and mean [corrected] duration of therapy of 4.0 and 12.6 months, respectively, patients presented with acute renal failure (mean creatinine 3.5 mg/dl) and nephrotic-range proteinuria (mean 24-hour urine protein 9.7 g). Renal biopsy revealed collapsing FSGS with extensive foot process effacement and many endothelial tubuloreticular inclusions. Follow-up was available for 10 patients, all of whom discontinued IFN. At a mean of 23.6 months, nine of 10 patients had improvement in renal function, including one with complete remission and two with partial remission. Among the seven patients with available data, mean proteinuria declined from 9.9 to 3.0 g/d. Four of the seven patients were treated with immunosuppression, and there was no detectable benefit. CONCLUSIONS Collapsing FSGS may occur after treatment with IFN-alpha, -beta, or -gamma and is typically accompanied by the ultrastructural finding of endothelial tubuloreticular inclusions. Optimal therapy includes discontinuation of IFN.

Glomerular disease related to anti-VEGF therapy

CASE PRESENTATION A 59-year-old Caucasian woman presented with a 5-month history of worsening renal insufficiency, proteinuria, and increasing leg edema. Serum creatinine on admission was 3.3 mg/100 ml (estimated glomerular filtration rate 15 ml/min). Baseline serum creatinine 7 months previously was 0.9 mg/100 ml. There was no history of diabetes or hypertension and no family history of renal disease. The patient was diagnosed with metastatic mammary ductal adenocarcinoma in 1993 and underwent radical mastectomy, radiation therapy, and several courses of chemotherapy. Her regular medications included

Giant Cell Tubulitis With Immune Complex Deposits in a Patient With Lupus Nephritis

We report a case of acute tubulointerstitial nephritis with giant cell tubulitis and tubular basement membrane immune complex deposits in a patient with membranous lupus nephritis. The patient, who had no prior evidence of lupus nephritis, developed acute kidney failure and mild proteinuria after cardiac valve replacement surgery. Giant cell tubulitis with tubular basement membrane immune complex deposits has been described in 4 patients after cardiac surgery, 3 of whom received cefuroxime, suggesting the possibility of a drug hypersensitivity reaction. The present case suggests there may also be a pathogenetic role for autoimmunity in this condition.

Association between Reperfusion Renal Allograft Biopsy Findings and Transplant Outcomes

Biopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0-3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation-related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.

Classification Systems in Renal Pathology Promises and Problems

Kidney diseases are morphologically heterogeneous. Pathologic classifications of renal disease permit standardization of diagnosis and may identify clinical-pathologic subgroups with different outcomes and/or responses to treatment. To date, classifications have been proposed for lupus nephritis, allograft rejection, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic antibody -related glomerulonephritis, and diabetic glomerulosclerosis. These classifications share several limitations related to lack of specificity, reproducibility, validation, and relevance to clinical practice. They offer a standardized approach to diagnosis, however, which should facilitate communication and clinical research.

The Diagnosis of Minimal Change Disease in Diabetic Nephropathy

Proteinuria is common in diabetic patients and usually reflects the presence of diabetic glomerulosclerosis. This paper reviews the differential diagnosis of proteinuria in diabetic patients and discusses the role of renal biopsy examination in identification and management of minimal change disease in this cohort. Identification of nondiabetic glomerular disease requires careful correlation of clinical history and renal biopsy findings and may have important implications for prognosis and therapy.

Atypical Antiglomerular Basement Membrane Disease With IgG1-κ Staining

INTRODUCTION A ntiglomerular basement membrane (GBM) disease is an autoimmune disease that classically presents as a rapidly progressive crescentic glomerulonephritis, with or without pulmonary hemorrhage, and typically does not relapse. The anti-GBM autoantibodies, typically polyclonal IgG1 and IgG4, bind to the noncollagenous 1 domain of the alpha-3 chain of type IV collagen that is present on alveolar and glomerular basement membranes. Kidney biopsies in patients with anti-GBM disease reveal a crescentic and necrotizing glomerulonephritis on light microscopy with diffuse linear staining of the glomerular basement membrane for IgG on immunofluorescence (IF) microscopy. Anti-GBM antibodies are detectable in the serum of w90% of patients using conventional enzyme-linked immunosorbent assays. Atypical antiGBM disease is a rare entity defined by uncharacteristic histologic features on light microscopy and/or linear GBM staining for an antibody other than the typical polyclonal IgG on IF. Here we describe a case of relapsing, atypical IgG1-k anti-GBM glomerulonephritis.

Delayed spontaneous resolution of nephrotic syndrome in a patient with hepatitis C virus-associated membranoproliferative glomerulonephritis.

Treatment with antiviral and/or immunosuppressive therapy is considered the standard care in patients with hepatitis C virus (HCV)-associated membranoproliferative glomerulonephritis (MPGN). However, even with an adequate therapy, a favourable response is not always guaranteed. In patients with HCV-associated MPGN, a delayed spontaneous remission of nephrotic syndrome is rare. We present here one such case. Our patient refused antiviral (and immunosuppressive) therapy throughout the course of his illness and was thus managed symptomatically. More than 8 months after presentation, an unexpected gradual resolution of his nephrotic syndrome was noted. The urine protein/creatinine ratio decreased from ~16 000 mg/g of creatinine on presentation to 500 mg/g of creatinine in the 12th month. This was however not accompanied by resolution of HCV or cryoglobulinaemic activity. Our case demonstrates the possibility of a delayed spontaneous remission occurring in this disease. This must be considered when weighing treatment options in such patients.