Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain-restricted immunoglobulin and is rarely reported in children. METHODS: We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition. RESULTS: Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-λ, two showed IgG3-κ, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course. CONCLUSIONS: Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID. Graphical abstract.

Urgent Start Peritoneal Dialysis: A Population-Based Cohort Study.

Rationale & Objective: It is a common practice to start patients in urgent need of dialysis on hemodialysis via a central venous catheter. Because central venous catheter use is associated with increased risk of infections, hospitalizations, and mortality, urgent start peritoneal dialysis (PD) increasingly represents a viable alternative. This study aimed to examine clinical outcomes, complications, mortality, and modality retention in patients who initiated urgent start PD. Study Design: Retrospective cohort study. Setting and Participants: Eighty-four adult members of a large integrated health care system who initiated urgent start PD between January 1, 2011, and December 31, 2014. Exposure: Urgent start PD. Outcomes: Retention rates at 30, 90, and 365 days; time to the development of noninfectious and infectious complications, modality failure, and all-cause mortality. Analytical Approach: Cumulative incidence of all-cause mortality was estimated using the Kaplan-Meier method. Retention rates for PD were computed using binomial proportions. Results: Occurrence of major complications was less than 5%. Catheter malfunction occurred in 6% of cases; of those, catheter patency could be established in 80%. Infectious complications occurred in 20% of patients who initiated PD and included peritonitis and exit site infections. At 365 days after initiation, the cumulative incidence of all-cause mortality was 9.7% (95% CI, 4.7%-19.4%). PD retention rates were 98.8%, 91.3%, and 80.0% at 30 days, 90 days, and 1 year, respectively. Limitations: Retrospective cohort design, a well-matched comparable group of urgent start hemodialysis patients could not be identified, small number of patients in a single integrated health care system, uncertain or limited generalizability of findings to other health care systems. Conclusions: At 1 year after initiation, patients who initiated urgent start PD had high survival and modality retention rates. In unplanned initiation of dialysis, urgent start PD is a viable and sustainable option and should be considered in selected patients to optimize care.

A case report of paraproteinemia-associated pauci-immune glomerulonephritis - a new form of monoclonal gammopathy of renal significance?

BACKGROUND: Renal disease associated with paraproteinemias is classically predicated upon pathologic paraprotein deposition in the kidney. However, growing evidence suggests that paraproteins may be able to systemically activate complement or neutrophils to drive renal damage. This may provide an alternative pathologic mechanism for renal injury in rare cases. CASE REPORT: We report a case of a patient with crescentic pauci-immune glomerulonephritis presenting with rapidly progressive renal failure, polyarthropathy, and a purpuric rash in association with a monoclonal immunoglobulin G κ-light-chain producing multiple myeloma. Serum anti-neutrophil cytoplasmic antibodies were not detected. Kidney biopsy, including with Pronase digestion, did not reveal pathologic paraprotein deposition. Two previously published similar case reports are also discussed. CONCLUSION: We propose a novel pathologic mechanism involving monoclonal proteins as a trigger for pauci-immune glomerulonephritis, potentially via complement dysregulation and/or neutrophil activation. This requires further epidemiologic and mechanistic study.

The role of kidney biopsy in heart transplant candidates with kidney disease.

BACKGROUND: Kidney disease is common in patients with advanced heart failure and can result from intrinsic parenchymal disease or to reversible hemodynamic factors. Distinguishing the two is difficult but is important when selecting patients who will benefit from combined heart and kidney transplantation (HKT) versus heart transplantation (OHT) alone. The goal of this study was to characterize kidney biopsy findings in this population and follow the outcome of patients based on the biopsy results. METHODS: Thirty heart transplant candidates with an estimated glomerular filtration rate less than 40 mL/min or proteinuria greater than 500 mg/day or a history of amyloidosis underwent kidney biopsies between June 2001 and March 2009. The renal pathologic diagnosis as well as the percent tubular atrophy and interstitial fibrosis on renal biopsy were assessed. RESULTS: Proteinuria and glomerular filtration rate at the time of evaluation for heart transplant did not correlate with the degree of fibrosis on biopsy. On the basis of the biopsy results, nine patients were listed for OHT and eight patients were listed for HKT. One patient originally triaged to receive OHT and was listed for HKT due to subsequent worsening of renal function. Eight patients received OHT, none required dialysis during a median follow-up period of 18 months. CONCLUSIONS: Renal biopsy provides useful diagnostic information to differentiate intrinsic renal disease from renal hypoperfusion and helps guide the decision for OHT alone versus combined HKT.