Clinical Response to Intestine-targeted Steroid Therapy in Biopsy-proven Immunoglobulin A Nephropathy.

Primary immunoglobulin A (IgA) nephropathy is associated with a dysfunctional mucosal immune system, leading to renal deposition of IgA and injury. Fifty patients with biopsy-proven IgA nephropathy were included. All patients were initiated on renin-angiotensin-aldosterone system (RAAS) inhibitors, polyunsaturated fatty acids, and a controlled release formulation (CRF) of budesonide. All drugs were started together, as isolated RAAS inhibitors will not prevent the immunological damage caused by the ongoing deposition of IgA. Depending on the histology (mesangial hypercellularity, endocapillary proliferation, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescents score), the patients received 9 mg or 12 mg of budesonide. All patients were followed up every 4 weeks to monitor renal function, 24-h urinary protein, and adverse effects. Our primary outcome was a mean change in the estimated glomerular filtration rate (eGFR) and 24-h urinary protein from the baseline to the end of 6 months. The percentage of decline in mean 24-h protein at 6 months from the baseline was 33%. The mean decrease in serum creatinine from the baseline was 0.73 mg/dL. The mean gain in eGFR from the baseline was an increase of 9 mL/min/1.73 m2. Of 50 patients, 11 (22%) achieved complete remission, 20 (40%) achieved partial remission, and 16 (32%) were non-responders. Three patients (6%) were lost to follow-up. The early initiation of CRF budesonide with optimized supportive care led to reductions in proteinuria and improvements in eGFR at 6 months in patients with IgA nephropathy. Early lesions with minimal chronicity showed an excellent response to budesonide.

Successful treatment of a patient with posttransplant IgA nephropathy with targeted release formulation of budesonide.

Recurrence of glomerulonephritis is the third-leading cause of allograft loss. Graft loss due to IgA nephropathy occurs in 10% at 10-year follow-up. The NEFIGAN trial demonstrated that Target Release Formulation (TRF) of budesonide is a specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation with favorable safety profile. We are reporting a case of successful treatment of a patient with posttransplant IgA nephropathy with TRF of budesonide.

Recurrence of membranoproliferative glomerulonephritis post transplant - Is this mere recurrence of pattern or recurrence of disease?

Recurrence of membranoproliferative glomerulonephritis (MPGN) is seen in 1965% cases of postrenal transplant resulting in graft loss in up to 35-50% of cases. A 31-year-old female, after 1% years on maintenance hemodialysis, underwent ABO compatible deceased donor kidney transplantation with basiliximab induction. During the immediate posttransplant period, the patient had delayed graft function, but achieved nadir creatinine of 0.9 mg/dL by 10 days. Nine months posttransplant, the patient developed fever, anasarca, and decrease in urine output with albuminuria 3+, active sediments in urine, serum creatinine 3.5 mg/dL, 24-h urine protein 7.5 g, and low C3. The patient underwent graft biopsy. Subsequently, the patient received pulse steroid for three days and five sessions of plasmapheresis. Renal biopsy report was suggestive of MPGN with focal crescents and acute tubular necrosis. Immunofluorescence showed Ig G3+, C3 3+, к 3+, and negative for λ or other immunoglobulins or complements. As her native kidney disease was immune-complex-mediated MPGN with no light chain restriction, paraffin tissue of the native kidney was reexamined for light chain restrictions by immunoperoxidase method, but did not show light chain restriction. The patient underwent extensive workup for paraproteinemias, but results were negative. Subsequently, she received four doses of bortezomib. The patient's serum creatinine got reduced to 0.8 mg/dL and proteinuria reduced to 800 mg/day. Our case is unique as we were not able to demonstrate monoclonal deposits in native kidney sample although there was recurrence of MPGN with monoclonal light chain deposits post transplant. Our findings emphasize the need for thorough evaluation of paraproteinemias in patients with idiopathic MPGN even in the absence of light chain deposition in biopsy.

A "Mini-Epidemic" of anti-glomerular basement membrane disease: Clinical and epidemiological study.

Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM) antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17-80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5-7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.

A case of primary renal allograft dysfunction due to myeloma cast nephropathy.

We report a rare case of primary renal allograft dysfunction due to myeloma cast nephropathy in a patient with no overt clinical features of multiple myeloma preceding his transplantation. A 45-year-old man on hemodialysis for six months for end-stage kidney disease due to presumed chronic glomerulonephritis developed immediate graft dysfunction post-transplantation. The graft biopsy was diagnostic of myeloma cast nephropathy. Other criteria for lambda light chain multiple myeloma were fulfilled with immunofixation electrophoresis and bone marrow biopsy. He was treated with plasmapheresis, bortezomib and high-dose dexamethasone. However, the patient succumbed to septicemia on the 37 th post-operative day. This is probably the first report of primary renal allograft dysfunction due to myeloma cast nephropathy diagnosed within the first week post-transplanation in a patient with unrecognized multiple myeloma.

Opportunistic infections in a renal transplant recipient.

With the present progress in transplantation procedures, there is an improvement in patient and allograft survival. However, the immunosuppression necessary to sustain the allograft predisposes these transplant recipients to infection, which is now a significant cause of morbidity and mortality. We describe a case of a 30-year-old renal transplant recipient with two opportunistic infections, namely, primary cutaneous aspergillosis and intestinal tuberculosis, with terminal enterococcal pleuritis and peritonitis. Control of the degree of immunosuppression, and prompt recognition and treatment of infection are vital for successful organ transplantation.