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Nephronophthisis by Light Microscopy

Nephronophthisis is an autosomal recessive tubulointerstitial nephropathy that is a leading genetic etiology of end-stage renal disease in children and young adults. Approximately 60% of patients with a known genetic etiology of nephronophthisis are due to homozygous deletion of the NPHP1 gene. The histopathologic lesions associated with nephronophthisis are shown in these photomicrographs. (A) A tubular floret profile with complicated tubular branching in at least 4 directions (PAS; original magnification ×400). (B) Macula densa-like lesions (arrows) are tubular profiles in which there is a transition to a grouping of cells with crowded, hyperchromatic nuclei and a high nuclear: cytoplasmic ratio...

Nephronophthisis by ISH

Nephronophthisis is an autosomal recessive tubulointerstitial nephropathy that is a leading genetic etiology of end stage renal disease in children and young adults. Approximately 60% of patients with a known genetic etiology of nephronophthisis are due to homozygous deletion of the NPHP1 gene. Fluorescence In-Situ Hybridization is both sensitive and specific for the detection of NPHP1 deletion in renal biopsies suspected to represent nephronophthisis. (A) Cases without NPHP1 deletion show nuclear profiles (DAPI blue) with two probe signals for both the control centromeric probe CEP2 (FITC green) and NPHP1 (CY3 orange). An arrow indicates a nuclear profile with two signals of...

Chronic Lesions of ANCA – Fibrous Crescent

Fibrous crescents can be differentiated from ischemic obsolescent glomeruli based on the pattern of global sclerosis. The fibrous crescent has interruption of the sclerotic glomerular tuft by fibrosis as is shown in photomicrograph A. By comparison, the ischemic obsolescent glomerulus in photomicrograph B shows a retracted glomerular tuft surrounded (but not transected by) fibrosis.

Light Chain Deposition Disease

The immunofluorescence in cases of monoclonal immunoglobulin deposition disease is characterized by linear tubular basement membrane staining. In these cases, the positive staining is restricted to the monoclonal immunoglobulin leading to disease. The photomicrographs here show strong staining for kappa compared to lambda in a case of kappa light chain deposition disease. There is also commonly staining of the interstitium, vessels, and glomeruli. When the monoclonal immunoglobulin is a heavy chain, the immunofluorescence shows strong staining for the depositing heavy chain with little to no staining for either light chain.

Proliferative Glomerulonephritis with Monoclonal IgG Deposits

This renal biopsy from a 57-year-old male with acute renal failure, hematuria, and nephrotic-range proteinuria shows a proliferative glomerulonephritis (A) with IgG kappa-restricted deposits by immunofluorescence. These findings are consistent with the entity known as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID). Approximately 30% of patients with these renal biopsy findings prove to have an associated monoclonal immunoglobulin in the serum. However, the underlying etiology in the majority of these cases is undetermined as most do not have evidence of infection, autoimmune disease or hematologic malignancy.

Light Chain Proximal Tubulopathy Without Crystals Tutorial

The two most common morphologic variants of light chain proximal tubulopathy (LCPT) are LCPT with and without crystal formation. The histopathologic features of light chain proximal tubulopathy without crystal formation are shown here. (A) The tubular epithelium in this case shows evidence of acute tubular injury with reactive nuclei and cytoplasmic thinning (hematoxylin and eosin; original magnification × 400). (B) Transmission electron photomicrograph of proximal tubule cytoplasm showing lysosomes with an irregular mottled appearance and no evidence of crystal formation (unstained; original magnification × 20,000). (C and D) Serial sections stained with λ (C) and Κ (D) shows strong staining...

IgG4 Membranous

First identified in the pancreas as autoimmune pancreatitis, the IgG4-related disease is now known to affect many organs and body sites. Renal involvement may present as a discrete mass noted radiologically, or patients may present with renal failure secondary to diffuse sclerosing tubulointerstitial disease. Patients often have laboratory abnormalities that can support the diagnosis such as eosinophilia, low complement and hypergammaglobulinemia with an elevation of serum IgG4 levels. A combination of imaging, clinical and laboratory features, and histology are needed to make a definitive diagnosis. Patients often show a clinical and radiographic response to steroid therapy. The Jones methenamine silver...

IgA Nephropathy Oxford Scoring

The IgA nephropathy Oxford Classification was first published in 2009 by a working group of nephrologists and renal pathologists representing the Renal Pathology Society and International IgA Nephropathy Network. The lesions currently scored include mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubular atrophy/interstitial fibrosis, and cellular/fibrocellular crescent formation. Two of these lesions, crescent formation (A) and mesangial hypercellularity (B), are shown here.  For the purposes of the Oxford classification, mesangial hypercellularity is defined as >3 mesangial cell nuclei in a mesangial area not adjacent to the vascular pole (in sections cut to 3-micron thickness).

2,8 DHA Crystalline Nephropathy

The renal biopsy shown here has crystals present within the tubular lumens and cytoplasm with a brownish appearance by H&E (A) that are strongly silver positive on the Jones methenamine silver stain (B). The crystals are birefringent when viewed under polarized light (C).  These findings are characteristic of 2,8 DHA crystal deposition in the kidney resulting from a deficiency of adenine phosphoribosyltransferase. 2,8 dihydroxyadeninuria is an autosomal recessive disease resulting from pathogenic variants in the APRT gene. It is an important disease to recognize as treatment with a low purine diet and allopurinol therapy blocks formation of 2,8 DHA and...

PLA2R Tutorial

The diagnosis of membranous glomerulopathy has been transformed in the past 10 years with the discovery of PLA2R. PLA2R is the most common target antigen in cases of primary membranous glomerulopathy. Immunohistochemical staining for PLA2R (shown here) can detect the PLA2R type of membranous with high sensitivity and specificity. Recent studies have shown that serum testing for PLA2R antibodies can serve as a useful biomarker for monitoring the clinical activity of this disease.