Safety and utility of kidney biopsy in patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2.

AIM: Kidney biopsy (KBx) is the gold standard for evaluation of kidney disease, but is associated with a higher risk of complications in patients with reduced glomerular filtration rate (GFR). We studied the safety and utility of KBx in patients with eGFR <30 ml/min/1.73 m2 . METHODS: Consecutive adult patients with eGFR <30 ml/min/1.73 m2 , who were planned for a KBx and consented to participate were prospectively enrolled. Patients with solitary/transplant kidney or acute kidney injury were excluded. Haemoglobin was checked on the day of KBx and repeated 18-24 h later along with a screening ultrasound. Post-KBx complications were noted and their risk-factors analysed. The utility of the KBx was graded as effecting significant, some, or no change to subsequent management. RESULTS: Of the 126 patients included, 75% were male, 27.7% were diabetic, and the median eGFR was 13.5 ml/min/1.73m2 . Major complications occurred in 5.6%. Peri-renal haematomas were detected in 37.3%, and haematomas ≥2 cm were significantly more frequent in those with eGFR <15 ml/min/1.73 m2 (29.2% vs. 13%, p = .032). Dialysis was a risk factor, while pre KBx blood transfusion, diabetes and higher serum albumin were protective against any complication. KBx was more likely to make a significant difference in management in those with eGFR 15-29 ml/min/1.73m2 (44.1% vs. 11.1%, p < .001). Increasing age, lower serum creatinine and albumin were independently associated with KBx utility. CONCLUSION: KBx is relatively safe in severe kidney disease but its risk to benefit balance needs to be carefully considered when eGFR is <15 ml/min/1.73m2 .

Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI- Glomerular Research And Clinical Experiments- Ig A Nephropathy in Indians-cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.

Multiloculated Cystic Renal Tumors of Childhood: Has the Final Word Been Spoken.

BACKGROUND: Multicystic renal tumors which include cystic nephroma, cystic partially differentiated nephroblastoma (CPDN) and cystic Wilms tumor has been a diagnostic and therapeutic challenge. Histopathological examination has been the only reliable differentiating method. Management of these tumors is still riddled with controversy as a definitive preoperative differentiation between the three has not been possible. METHODS: A retrospective evaluation was performed of the treatment strategies employed with nine cases of multicystic renal tumors treated from 2005 to 2015. RESULTS: The median age at presentation was 12 months with all except one being boys. All except two children underwent primary surgery. The median follow-up was 50 months with six children having long-term survival. One child succumbed to the disease process, one died due to an unrelated cause and another was lost to follow-up. Although there was no ambiguity with cases of cystic nephroma (CN) and cystic Wilms tumor, three of the four cases of CPDN had problems. CONCLUSION: Primary surgery for multicystic renal tumors is safe and should be seriously considered as it prevents overtreatment in cases of CN and early stage CPDN. Further studies are needed to fully understand the biological behavior of CPDN.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre.

AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.

Immunohistochemical Glomerular Expression of Phospholipase A2 Receptor in Primary and Secondary Membranous Nephropathy: A Retrospective Study in an Indian Cohort with Clinicopathological Correlations.

BACKGROUND: Limited published literature exists on the utility and standardization of anti-phospholipase A2 receptor (anti-PLA2R) immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy (MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN and clinicopathological correlations in an Indian cohort. METHODS: Subjects included patients with primary and secondary MN diagnosed between January 2012 and August 2014 with an adequate renal biopsy and at least 1 year of clinical follow-up. Anti-PLA2R IHC was performed in all cases with miscellaneous renal lesions as controls. Electron microscopy was performed in selected cases. Sensitivity and specificity of anti-PLA2R IHC to identify primary MN was evaluated. Histopathological analyses of primary and secondary MN were done with clinicopathological correlations including serum creatinine, eGFR, chronic kidney disease stage, 24-h urine protein, serum cholesterol, serum albumin, and hypertension at presentation and follow-up, using the Kruskal-Wallis test and Spearman rank correlation. A p value of ≤0.05 was considered statistically significant. RESULTS: In 153 MN patients (99 primary, 54 secondary) and 37 miscellaneous controls, anti-PLA2R IHC differentiated primary from secondary MN with a sensitivity of 70.2% and a specificity of 96.6%. Secondary MN had increased mesangial matrix expansion compared to primary MN (p = 0.001). Severe nephrotic syndrome, impaired renal function, and hypertension were all more common in primary than in secondary MN. CONCLUSION: Anti-PLA2R IHC is a specific marker to distinguish primary MN from secondary MN.

Leukocyte Derived Chemotaxin 2 (ALECT2) Amyloidosis.

We describe the first case from India of ALECT2 amyloidosis. An adult Punjabi male presented with progressive renal dysfunction and non-nephrotic range proteinuria. Serum protein electrophoresis and immunofixation were normal, with mildly elevated serum free light chain ratio. A renal biopsy confirmed the presence of amyloid. Immunohistochemistry was negative for monoclonal light chains. Proteomic analysis confirmed the presence of ALECT2 amyloid. The present case highlights the need for confirmatory testing for typing of amyloid.

Cushing's syndrome in a case of thymic carcinoma.

A 29-year-old gentleman presented with episodic features suggestive of Cushing's syndrome. He was evaluated and diagnosed with ectopic Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome due to a thymic tumor. The thymic lesion was excised and histopathology confirmed thymic carcinoma with neuroendocrine differentiation, with local, perineural, and vascular invasion. The postoperative problems and further treatment options have been discussed in this case report.

Cryptococcal granulomatous interstitial nephritis and dissemination in a patient with untreated lupus nephritis.

Infection is a significant cause of mortality and morbidity in systemic lupus erythematosus (SLE). There are many reports of cryptococcal infection in patients with SLE, on immunosuppression. However, untreated lupus with cryptococcal infection and dissemination is rare. CD4 lymphopaenia is not reported in such patients. We describe a patient with untreated SLE to be having cryptococcal granulomatous interstitial nephritis and dissemination with CD4 lymphopaenia.

Chromophobe renal cell carcinoma: A report of two cases with unusual histological features.

We report two cases of chromophobe renal cell carcinoma with unusual histological features; one case of eosinophilic variant of chromophobe renal cell carcinoma and another case with extensive metaplastic ossification.

Multicentric small cell neuroendocrine neoplasm of the renal pelvis and ureter with concomitant focal high-grade urothelial carcinoma of the ureter: A case report.

Malignant small cell neuroendocrine tumors of the pelvi-calyceal system are rare, and even more uncommon is their occurrence with concomitant transitional cell carcinoma, in the same renal unit. We present such a case for its unique presentation.

Characterization of kidney lesions in Indian adults: towards a renal biopsy registry.

BACKGROUND: In the absence of a renal biopsy registry, there is a paucity of data on the renal disease pattern seen in India. This study reviews the changing pattern of renal disease seen at a single center over the last 30 yrs. METHODS: Histopathological data of 5415 adequate native kidney biopsies performed on consecutive adult Indian patients presenting to our hospital from 1986-2002 were analyzed. This pathological demography classified according to the modified World Health Organization (WHO) classification was compared to the earlier published cohort collected from 1971-1985 (n=2827) to ascertain the changing trends. RESULTS: The indications for renal biopsy were comparable between the cohorts and included nephrotic syndrome (65%), nephritic syndrome (13%) and chronic renal failure (10.2%). Primary glomerular disease accounted for 71% of all biopsies. Non-immunoglobulin A (IgA) mesangio proliferative glomerulonephritis as a group was the predominant pathology (20.2%), followed by idiopathic focal segmental glomerulosclerosis (FSGS) (17%), minimal change disease (MCD) (11.6%), membranous glomerulopathy (MN) (9.8%), IgA nephropathy (8.6%) and membranoproliferative glomerulonephritis (MPGN) (3.7%). Of the patients with secondary kidney diseases, lupus nephritis (6.5%), diabetic nephropathy (2.5%), interstitial nephropathy (2.5%) and benign nephrosclerosis (2.2%) were notable. During the 31 yrs of the study period, there was a steady increase in FSGS prevalence (p<0.001), MN (p<0.0001), and post infectious glomerulonephritis (PIGN) (p<0.001). A reduction in the frequency of MPGN (p<0.001) and MCD (p<0.001) was observed. CONCLUSIONS: This is the largest series of renal biopsy data from India; and therefore, could reflect the demographic picture of renal diseases in this country. It discusses evolving patterns over 30 yrs and highlights differences with the developed world. This report represents the basis for the future of a renal biopsy registry in India.

Presentation, prognosis and outcome of IgA nephropathy in Indian adults.

BACKGROUND: IgA nephropathy (IgAN) is not well characterized in India. This retrospective study of 478 patients with IgAN was performed to clarify the presenting features, prognostic factors and the renal survival rates of the disease. METHODS: Three hundred and forty-seven patients who had been followed on average for 27 months after diagnosis were divided into two groups based on renal function at diagnosis. In group 1 (229 patients), the creatinine clearance estimated by the Modification of Diet in Renal Disease formula was <85 mL/min and in group 2 (118 patients) it was >/=85 mL/min. RESULTS: The predominant modes of presentation were nephrotic syndrome, hypertension and renal failure. Twenty-nine percent of patients had more than a 20% decline in renal function at the last follow up. Multivariate analyses with stepwise logistic regression identified hypertension (odds ratio (OR) 3.5), nephrotic range proteinuria (OR 3.4) and sclerosed glomeruli on biopsy (OR 4.1) to be independently associated with progression in group 1 and hypertension (OR 2.3) in group 2. Seventeen percent of patients progressed to end-stage renal disease (ESRD). Using multivariate analysis by the Cox model, four risk factors for developing ESRD were identified: hypertension (hazard ratio (HR) 3.1); nephrotic proteinuria (HR 1.9); interstitial fibrosis (HR 2.5); and sclerosed glomeruli (HR 1.8). The renal survival rates at 1, 5 and 10 years were 84, 55 and 33%, respectively, with a median renal survival of 61 months from the time of biopsy. CONCLUSION: The relatively rapid rate of progression of IgAN in India is suggestive towards a 'malignant' nature of the disease in this country.

Chondrosarcoma of the nasal septum.

Chondrosarcoma of the head and neck region are relatively uncommon, arising rarely in the naval septum. The reported cases of nasal septal chondrosarcomas are extensive lesions with involvement of paranasal sinuses, orbit or skull base at the lime of diagnosis. Those limited to the nasal cavity is extremely rare and to date there has been one case report in English language literature. We present a case of chondrosarcoma of the nasal septum with involvement of the nasal cavity alone and no evidence of bony erosion. Initial multiple biopsies showed mature chondromatous areas with no atypia. The patient had wide excision of the tumour. The final biopsy of the excised specimen revealed foci of well-differentiated chondrosarcoma. Wide surgical excision with adequate margins should be considered as the treatment of choice in lesion of nasal septum even if initial biopsies are negative for malignancy. Hence this case report.