Sustained remission of antineutrophil cytoplasmic antibody-mediated glomerulonephritis and nephrotic syndrome in mixed connective tissue disease.

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.

Renal medullary angiitis: a case series from a single institution.

Renal medullary angiitis is a lesion involving the vasa recta of the medulla. The characteristic morphologic findings on renal biopsy include interstitial hemorrhage with associated polymorphonuclear leukocyte infiltration and karyorrhectic debris. A total of 18 cases have been described in three publications, all in the setting of antineutrophil cytoplasmic antibody (ANCA)-associated disease. We sought to detail the morphology and clinical significance of this lesion. A total of 38 cases of medullary angiitis were identified in our case files from January 2008 through August 2011. The clinical history was reviewed and pertinent information including patient age, gender, indication for biopsy, serum creatinine, and any positive serologic tests (ANCA) was collected for each biopsy. Cases with known and unknown ANCA status were reported separately. In total, 19 (63%) of 30 cases of medullary angiitis with known ANCA antibody status were ANCA positive, whereas 11 (37%) of 30 were determined to be secondary to other etiologies. The most common non-ANCA etiology of medullary angiitis was immunoglobulin A nephropathy (20%) followed by antibiotic treatment in the setting of infection. In ANCA-unknown cases, 4 (50%) of 8 had pauci-immune crescentic glomerulonephritis. No cases had renal cortex involvement. This is the largest study to date detailing the morphology of medullary angiitis and the first to show medullary angiitis outside the setting of ANCA-associated disease. It is an important lesion to recognize as it frequently suggests the presence of a systemic vasculitis and could be mistaken for interstitial nephritis.

Symptomatic anti-neutrophil cytoplasmic antibody-positive disease complicating subacute bacterial endocarditis: to treat or not to treat?

A 54-year-old man was diagnosed with Streptococcus mutans endocarditis of the mitral valve. Serological tests disclosed the presence of multiple autoantibodies including c-ANCA, anti-PR3 and anti-MPO. While the fever subsided with antibiotics, mental status and renal function deteriorated rapidly. Kidney biopsy revealed pauci-immune glomerulonephritis and acute eosinophilic interstitial nephritis. The abnormal clinical features improved rapidly after addition of corticosteroids and cyclophosphamide to the antibiotics. Immunosuppressive agents may be required in a fraction of the patients with infective endocarditis who develop ANCA and ANCA-mediated renal disease. Histological identification of the type of renal disease is imperative for the choice of the treatment.

The morphologic spectrum and clinical significance of light chain proximal tubulopathy with and without crystal formation.

The renal diseases most frequently associated with myeloma include amyloidosis, monoclonal immunoglobulin deposition disease, and cast nephropathy. Less frequently reported is light chain proximal tubulopathy, a disease characterized by κ-restricted crystal deposits in the proximal tubule cytoplasm. Light chain proximal tubulopathy without crystal deposition is only loosely related to the typical light chain proximal tubulopathy, and little is known about this entity. A search was performed of the 10 081 native kidney biopsy samples processed by our laboratory over the past 2 years for cases that had light chain restriction limited to the proximal tubule cytoplasm. A total of 10 cases of light chain proximal tubulopathy without crystal deposition were found representing 3.1% of light chain-related diseases. Nine of these 10 showed λ-light chain restriction. Only three cases of light chain proximal tubulopathy with crystals were found accounting for 0.9% of light chain-related diseases. Two of these three were κ subtype. Plasma cell dyscrasia was unsuspected in seven of the 10 patients with light chain proximal tubulopathy without crystals at the time of renal biopsy. After the biopsy was reported, follow-up was available on 9/10 patients with 9/9 showing a plasma cell dyscrasia including 8/9 with multiple myeloma. We found that light chain proximal tubulopathy without crystal formation, despite being rarely described in the literature, is over three times more common than light chain proximal tubulopathy with crystal formation in our series. And given that it is often associated with previously unrecognized myeloma, it is a critically important diagnosis.

C1q nephropathy and minimal change nephrotic syndrome.

C1q nephropathy (C1qN) is an uncommon disorder seen in children and adults with nephrotic syndrome and non-specific urinary findings. It has been described with minimal change nephrotic syndrome (MCNS), focal segmental glomerulonephritis and isolated mesangial proliferative glomerulonephritis. We describe nine children with MCNS and mesangial C1q deposition. These children had a median age of 2.7 years at diagnosis (range 1.3-15 years), 56% were male and 78% were Hispanic. We compared these children to concurrent patients with nephrotic syndrome and biopsy-proven MCNS. We found that the C1qN patients were more likely than MCNS children to require chronic immunosuppression with calcineurin inhibitors or mycophenolate mofetil to maintain remission. However, all children were able to achieve and sustain clinical remission of nephrotic syndrome. Children with C1qN and minimal change histology have an increased frequency of frequently relapsing and steroid-unresponsive disease, but they can attain prolonged remission and stable renal function with calcineurin inhibitor or mycophenolate mofetil therapy.

Epidemic of diabetic and nondiabetic renal disease among the Zuni Indians: the Zuni Kidney Project.

There is an epidemic of renal disease among the Zuni Indians. The prevalence of end-stage renal disease among the Zuni Indians is 18.4-fold and 7.4-fold higher than among European Americans and American Indians/Alaskan Natives, respectively. In contrast to other American Indian tribes, nondiabetic renal disease accounts for a significant percent of the renal disease burden among the Zuni Indians. To explore this hypothesis, a community epidemiologic study of the Zuni Pueblo was conducted. A questionnaire was administered, blood and urine samples were collected, and BP, height, and weight were measured. Neighborhood household clusters were used as the sampling frame to maximize ascertainment and minimize bias. Age and gender distributions in the sample (n = 1483) were similar to those of the eligible Zuni population (n = 9228). The prevalence, age-adjusted and gender-adjusted to the Zuni population, of incipient (0.03 < or = UACR < 0.3) albuminuria (IA) (15.0% [95% confidence interval, 13.1 to 16.9%]), and overt (UACR > or = 0.3) albuminuria (OA) (4.7% [3.6 to 5.8%]) was high. The prevalence estimates for IA and OA were higher among diabetic participants (IA: 33.6% [27.6 to 39.7%]; OA: 18.7% [13.7 to 23.7%]) than nondiabetic participants (IA: 10.8% [9.0 to 12.6%]; OA: 1.8% [1.0 to 2.5%]). However, there were more nondiabetic participants; therefore, they comprised 58.0% [51.4 to 64.6%] and 30.9% [20.0 to 41.7%] of participants with IA and OA, respectively. In contrast to most other American Indian tribes, nondiabetic renal disease contributes significantly to the overall burden of renal disease among the Zuni Indians.