Nephropathology (Renal pathology) is a subspecialty of anatomic pathology that deals with the diagnosis and characterization of medical diseases (non-tumor) of the kidneys. The department processes the renal biopsies (native and allograft) for light microscopy, immunofluorescence and electron microscopic evaluation by nephropathologist. Medical renal diseases present with varied clinical manifestations like nephrotic syndrome, nephritic syndrome, acute kidney injury, isolated hematuria/proteinuria and graft dysfunction, in the case of renal transplant recipient. These diseases may affect the glomerulus, the tubules and interstitium, the vessels, or a combination of these renal compartments. The nephropathologist analyses the findings of renal biopsy on light microscopy,immunofluorescence and electron microscopy keeping in mind the clinical findings to obtain a definitive diagnosis and to identify the particular renal compartment affected by the disease. In doing so he plays a pivotal role in the management of the patients with medical renal disease.

Renal biopsy- A Nephropathologist’s perspective:

Renal biopsy, a relatively safe medical procedure, has gained considerable importance for the diagnosis of medical renal diseases. Now-a-days, a spring-loaded automated cutting needle, with or without ultrasound guidance, is used for obtaining renal tissue core. Lower pole of native left kidney and most visible or accessible pole of transplanted kidney are utilized for renal biopsy. In adults, 14- or 16-gauge needles are suitable, considering the internal diameter of 900-1000 micron and 600-700 micron, respectively (average diameter of normal glomerulus in adult is 200-250 micron). Finer needle of 18-gauge (internal diameter 300-400 micron) may be used for children younger than 8 years.

Whenever possible, 2-3 cores of renal biopsy should be taken: one for light microscopy (LM), another for immunofluorescence (IF) and one for electron microscopy (EM), if required. These renal biopsy cores should be sent in separate vials containing appropriate fixative/transport media for each of these tests (Light microscopy- 10% Formalin, Immunofluorescence- Michel’s transport medium or normal saline, Electron microscopy- 2.5% Glutaraldehyde). The biopsies sent in normal saline should be processed within 6 hours. In cases where taking extra passes is not possible, a cutting protocol may be followed: both the ends of the core are taken for EM, one-third of the core, including some glomeruli, is placed in transport medium for IF and the rest is kept for LM.

The nephropathologist always works closely with nephrologists and transplant surgeons, who typically obtain diagnostic specimens via percutaneous renal biopsy. The absence of adequate pertinent clinical information seriously hinders with any meaningful evaluation of renal biopsy. Ideally, the renal biopsy should be accompanied by pertinent clinical information. Detailed clinical history, including past medical illnesses; recent laboratory values with particular emphasis on urinanalysis, biochemical parameters (urea, creatinine, total protein, cholesterol), serological investigations (ANA, dsDNA, ANCA, C3, C4, anti-GBM), viral markers (hepatitis B, hepatitis C, HIV) and other parameters of interest should be included. Details of any therapy administered should also be mentioned. In case of renal transplant biopsies, information must include duration of transplant and therapy. Nephropathologist, knowledgeable in both renal medicine and pathology and thus able to correlate subtle tissue-derived information with appropriate clinical data, remains the most important key to the development of an accurate clinicopathologic diagnosis. It needs to be remembered that renal pathology cannot succeed as a standalone practice. An extremely close collaboration and teamwork between nephrologist and nephropathologist is the key to achieving appropriate management of patients.

Adequacy of biopsy

The minimum diagnostic sample size varies with the specific diagnosis; for instance only one glomerulus is enough for making diagnoses such as membranous glomerulonephritis and amyloidosis, while 25 glomeruli may be required to make an accurate diagnosis of focal lesion like FSGS. For most of the light microscopic assessment, 8-10 glomeruli are considered adequate.

Nephropathology at NU hospitals

Nephropathology department has been started at NU hospitals from February 2015. A comprehensive evaluation of renal biopsies will be done by a qualified nephropathologist. The biopsies can be sent either in color coded vials provided by the NU hospitals or in separate vials containing appropriate fixative/transport media for each of these tests (Light microscopy- 10% Formalin, Immunofluorescence- Michel’s transport medium or normal saline, Electron microscopy- 2.5% Glutaraldehyde). Sample sent in normal saline should be accompanied with ice pack in case the transportation takes more than 6 hours. Courier service can be utilised for transport of samples from outstation. The reports will be dispatched via mail with pictures.

Sample transport requirements

For purposes of transport of patient samples, all clinical samples, in accordance with UN guidelines are generally classified as Category B and assigned to UN3373 (Biological Substance, Category B) and should be packaged in accordance with UN packaging instructions PI650.

Triple packaging system for transport of biopsy samples (with fixative) to lab-

The following procedures should be adopted for the transport of all specimens with fixative to the lab:

Step 1: Primary pack – should be water tight, leak proof, and labelled with patient detail and hospital name.

Step 2: Secondary pack – encloses primary pack(s), leak proof and water tight and protects the primary sample.

Step 3: Outer most pack: sealable & strong enough to protect contents from physical damage during transport.

Packaging for fresh biopsies (in normal saline without fixative)

Step 1: Primary pack – should be water tight, leak proof, and labelled with patient detail and hospital name.

Step 2: Secondary pack – encloses primary pack(s), leak proof, water tight and contains ice cubes to maintain cold chain in transit.

Step 3: Outer most pack: sealable & strong enough to protect contents from physical damage during transport.