Jonathan J. Hogan

The Native Kidney Biopsy: Update and Evidence for Best Practice

The kidney biopsy is the gold standard in the diagnosis and management of many diseases. Since its introduction in the 1950s, advancements have been made in biopsy technique to improve diagnostic yield while minimizing complications. Here, we review kidney biopsy indications, techniques, and complications in the modern era. We also discuss patient populations in whom special consideration must be given when considering a kidney biopsy and the important role that the kidney biopsy plays in nephrology training. These data are presented to develop best practice strategies for this essential procedure.

Drug-Induced Glomerular Disease: Immune-Mediated Injury

Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed.

Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab

Background/Aims: Rituximab and glucocorticoids are a non-inferior alternative to cyclophosphamide and glucocorticoid therapy for induction of remission in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients with moderate renal disease. The efficacy and safety of this approach in patients with severe renal impairment are unknown. We report the outcomes and safety profile of rituximab and glucocorticoid therapy for induction of remission in patients with AAV and ANCA-negative vasculitis presenting with severe renal disease. Methods: A multicenter, retrospective, cohort study was conducted between 2005 and 2014. Patients with new or relapsing disease with an estimated glomerular filtration rate (eGFR) of ≤20 ml/min/1.73 m2 treated with rituximab and glucocorticoid induction with or without plasmapheresis were included. Fourteen patients met the inclusion criteria. The primary outcomes were rate of remission and dialysis independence at 6 months. The secondary outcomes were eGFR at 6 months, end-stage renal disease (ESRD), survival rates and adverse events. Results: All patients were Caucasian, and 57% were male. The mean eGFR was 12 ml/min/1.73 m2 at diagnosis. All patients achieved remission with a median time to remission of 55 days. Seven patients required dialysis at presentation of which 5 patients recovered renal function and discontinued dialysis by 6-month follow-up. The mean eGFR for the 11 patients without ESRD who completed 6-month follow-up was 33 ml/min/1.73 m2. Four patients ultimately developed ESRD, and one died during the follow-up period. Conclusion: Patients with AAV and severe renal disease achieve high rates of remission and dialysis independence when treated with rituximab and glucocorticoids without cyclophosphamide.

Development of proteinuria and focal segmental glomerulosclerosis during direct-acting antiviral therapy for hepatitis C virus infection

Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic diagnosis made in patients with proteinuria who exhibit focal glomerular scarring and podocyte injury on kidney biopsy and is associated with high rates of renal disease progression over time. We recently observed 3 patients with hepatitis C virus (HCV) infection, solid organ transplantation, and normal baseline kidney function who developed proteinuria during treatment with direct-acting antiviral (DAA) therapies and whose kidney biopsies demonstrated FSGS without immune complex or cryoglobulinemic glomerulonephritis (Table 1).

Hemophagocytic Syndrome With Histiocytic Glomerulopathy and Intraglomerular Hemophagocytosis

Hemophagocytic syndrome (HPS), a rare and life-threatening disease, is characterized by hyperactivation of the immune system that causes hypercytokinemia and potential multiorgan failure. Acute kidney injury is the most common kidney manifestation of HPS and is generally considered a poor prognostic factor. Glomerular involvement is uncommon and usually manifests as either podocytopathy with collapsing glomerulopathy or thrombotic microangiopathy. We report a rare case of severe histiocytic glomerulopathy in a patient with HPS who presented with acute kidney injury and proteinuria. Kidney biopsy revealed massive glomerular infiltration by macrophages resembling proliferative glomerulonephritis accompanied by intraglomerular hemophagocytosis and mild features of glomerular thrombotic microangiopathy. The patients kidney failure and proteinuria responded rapidly to high-dose pulse methylprednisolone followed by a tapering course of oral prednisone. Our case expands the renal pathologic spectrum of HPS to include histiocyte-rich glomerular infiltration and intraglomerular hemophagocytosis. Greater awareness of this entity is needed to ensure prompt recognition and appropriate 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.

New-onset hepatitis C virus-associated glomerulonephritis following sustained virologic response with direct-acting antiviral therapy

Glomerulonephritis (GN) is an important extra-hepatic manifestation of infection with hepatitis C virus (HCV). HCV-associated GN occurs due to HCV-induced lymphoproliferation, leading to the generation of pathogenic immune complexes, including complexes containing cryoglobulins. The management of HCV-associated extra-hepatic disease is focused on viral eradication, with direct-acting antiviral agents leading to high rates of sustained virologic remission. There have been a few reports of relapsing cryoglobulinemic vasculitis after sustained virologic remission was achieved with interferon-based therapies. This report presents two cases of new-onset HCV-associated GN that occurred after sustained virologic response was achieved with direct-acting antiviral (DAA) therapy.
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A clone-directed approach may improve diagnosis and treatment of proliferative glomerulonephritis with monoclonal immunoglobulin deposits

The optimal treatment for the monoclonal gammopathies of renal significance is not known, but there is consensus among experts that treatment should be specific for the underlying clone. The majority of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) do not have an identifiable clone, and prior studies have found poor renal outcomes for patients with PGNMID treated with a variety of regimens. Here we present a retrospective case series of 19 patients with PGNMID with a more uniform, clone-directed approach. A circulating paraprotein was detected in 37% of patients, and the overall clone detection rate was 32%. Treatment was directed at the underlying clone or, for patients without a detectable clone, empirically prescribed to target the hypothesized underlying clone. Of the 16 patients who underwent treatment, the overall renal response rate was 88%, and 38% of patients experienced complete renal response (proteinuria reduction to under 0.5 gm/24 hours) with initial treatment. All patients were End Stage Renal Disease-free at last follow-up (median 693 days after diagnosis), and treatment was well tolerated. Thus, a clone-directed approach may lead to novel, targeted treatment strategies that could significantly improve outcomes for patients with PGNMID.

Heme-pigment nephropathy after transurethral resection of prostate cancer

Introduction: Transurethral resection of the prostate is one of the most common surgical procedures performed in men to relieve bladder outlet obstruction, most often due to benign prostatic hyperplasia. However, transurethral resection of the prostate may also be used in patients with metastatic prostate cancer who have bladder outlet obstruction. Acute kidney injury after transurethral resection of the prostate has been described and attributed to a variety of mechanisms, including acute tubular necrosis, rhabdomyolysis, and hemolysis with heme-pigment nephropathy. However, to our knowledge, no case of kidney biopsy-proven heme-pigment nephropathy due to hemolysis from a transurethral resection of the prostate procedure has been published to date. Case description: We describe a case of an 82-year-old man with metastatic prostate cancer who presented with severe oliguric renal failure 2 weeks after transurethral resection of the prostate for bladder outlet obstruction. Laboratory studies showed evidence of hemolysis, and a kidney biopsy showed heme-pigment cast nephropathy. Conclusions: We hypothesize that the patient’s kidney injury was induced by hemolysis resulting from rapid absorption of hypotonic fluid administered during the transurethral resection of the prostate procedure. Patients with prostate cancer undergoing transurethral resection of the prostate for bladder outlet obstruction may experience severe complications related to rapid absorption of hypotonic fluid. Our case illustrates the importance of nephrology evaluation and kidney biopsy in patients with benign and malignant prostate conditions who experience post-transurethral resection of the prostate syndrome and acute kidney injury in order to better characterize these complications, and to develop preventative strategies for future cases.

A Case of Monoclonal Gammopathy of Renal Significance

A 53-year-old white man with a past medical history of gout and uric acid nephrolithiasis was referred for evaluation of proteinuria and CKD. His serum creatinine (SCr) had been 1.5–1.8 mg/dl for at least 3 years, and his urine dipsticks were positive for blood and protein, which had been