Uttara Das, KVDakshinamurty, Aruna P. Pattern of biopsy proven renal disease in a single center of South India: 19 years experience. Indian J Nephrol. 2011 Oct-Dec; 21(4): 250–257.

Abstract

The prevalence of biopsy-proven glomerulonephritis varies according to the geographic area, socioeconomic condition, race, age, demography and indication of renal biopsy. This study analyzed the distribution of biopsy-proven renal disease (BPRD) and its changing pattern over a period of 19 years from a tertiary care hospital in south India. All the renal biopsies performed from 1990 to 2008 were reviewed retrospectively. Biopsies were evaluated by light microscopy and immunofluorescence microscopy and also special stains when warranted. A total of 1849 biopsies were analyzed. The mean patient age was 32.27 ΁ 18.38 (range 10-80) years. The male:female ratio was 1.4:1. The most common indications of renal biopsy were nephrotic syndrome (49%), followed by chronic renal failure (13.6%) and rapidly progressive renal failure (12%).

Primary glomerulonephritis (PGN) comprised 1278 (69.1%) of the total patients. Among the PGN cases, the most common one was minimal change disease (21.8%), followed by focal segmental glomerulosclerosis [FSGS (15.3%)], membranous glomerulonephritis (10%), chronic glomerulonephritis (9.7%), postinfectious glomerulonephritis (8.1%), mesengioproliferative glomerulonephritis (7.5%), diffuse proliferative glomerulonephritis (6.7%), crescentic glomerulonephritis (6.5%), IgA nephropathy [IgAN (6.3%)], membranoproliferative glomerulonephritis (5.7%), focal proliferative glomerulonephritis (1.6%) and IgM nephropathy (0.5). Secondary glomerular disease (SGN) accounted for 337 (18.2%) of the cases. The most common SGN was lupus nephritis (80.1%), followed by amyloidosis (8%) and diabetic nephropathy (6.5%). Tubulointerstitial disease [124 (6.7%)] and vascular disease [60 (3.2%)] were less common. End-stage changes and miscellaneous disease were found in 37 (2%) and 13 (0.7%) cases, respectively. The incidence of FSGS and IgAN has been increasing since 1999. This study provides descriptive biopsy data and highlights the changing incidence of renal disease which is probably contributed by an increase referral due to increased awareness together with increased manpower and infrastructure.

Keywords: Epidemiology, glomerulonephritis, nephropathy, renal biopsy

Introduction

Renal biopsy is a definitive diagnostic test in patients with renal parenchymal disease. Indications of renal biopsy vary from center to center. Renal biopsy is useful for identifying the specific diagnosis, assessing the level of disease activity, and for allowing specific decisions about treatment to be made. The common clinical situations where biopsy is needed are nephrotic syndrome (NS), prolonged acute renal failure (ARF), rapidly progressive renal failure (RPRF), systemic diseases with renal dysfunction, non-nephrotic proteinuria, isolated microscopic hematuria, unexplained chronic renal failure (CRF), renal transplant dysfunction, and familial renal diseases.

Renal biopsy data analysis is essential to study the prevalence of biopsy-proven renal disease (BPRD) and its variation and distribution as per geographic areas, socioeconomic conditions, race, age and indication for renal biopsy, to understand the regional epidemiology of glomerular disease in a particular geographical region. It also improves the understanding of the utility of renal biopsy and acts as a framework for future research into renal parenchymal disease. Unfortunately, we do not have a central biopsy registry in India. Studies on the prevalence of renal disease in India are limited. Evidence from different published articles across the world indicates a changing pattern of glomerular disease over the last few decades. We have completed 19 years of collection of renal biopsy data at our center, a referral tertiary care teaching hospital in south India, and report the pattern of BPRD.

Uttara Das, KVDakhinamurty, Aruna P. M. S. Uppin. Nondiabetic Glomerular Diseas in Diabetic Patients: a single centre experiences in south India. Indian Journal of Nephrology. September 2012 / Vol 22 / Issue 5: 358-62

Abstract

Nondiabetic renal disease (NDRD) is seen as a cause of proteinuria and renal failure in type 2 diabetes mellitus (DM). The clinical differences between NDRD and diabetic glomerulosclerosis (DGS) are not clear. This study was done to find the spectrum of NDRD in type 2 DM patients and differences in clinical profile between NDRD and DGS patients. Data of patients with type 2 DM who underwent renal biopsy in this institute from 1990 to 2008 were analyzed retrospectively. Patients were categorized as isolated NDRD, NDRD with DGS, and isolated DGS.

A total of 75 patients were included. Mean age was 45 ± 10.2 years, male to female ratio was 3.1 : 1, median duration of DM was 12 months (range, 1 year-15 years), proteinuria was 4.2 ± 3.4 g/day, and serum creatinine was 4.3 ± 3.9 mg/dl. Hypertension was observed in 63 (84%) cases and microscopic hematuria in 24 (32%) cases. Nephrotic syndrome (38.7%) was the commonest clinical presentation. Forty-eight (64%) cases had NDRD and 27 (36%) had DGS. The commonest NDRD was minimal change disease (12.5%). Three (6.3%) patients had lupus nephritis.

Tubulointerstitial nephritis has been observed in 10.4% patients. No significant differences between NDRD and DGS patients were found except hypertension which was significantly high in the DGS group. Acute kidney injury and nephritic syndrome were not observed in the DGS group. In conclusion, the incidence of biopsy-proven NDRD in type 2 DM in this study was high. Kidney biopsy aided in the detection of NDRD in clinically suspected patients.

Keywords: Kidney biopsy, nondiabetic renal disease, type 2 diabetes

Introduction

Proteinuria in diabetic patients is usually interpreted as a clinical manifestation of diabetic nephropathy (DN). However, not all diabetic subjects with proteinuria have DN. Nondiabetic renal disease (NDRD) has been seen to cause proteinuria in diabetic patients. There is a wide variation of prevalence of NDRD. The occurrence of NDRD in type 1 diabetes mellitus (DM) is rare in comparison with those with type 2DM. Although exact incidence of NDRD is not known, frequency varies from 5% to 71% in various studies.

It is seen in 26.7% of Asian and 22% of European patients. Kidney biopsy is an unbiased method, but is seldom used in proteinuric diabetic patients. Olsen, in a meta-analysis of similar studies, found the frequency of glomerulonephritis (GN) to be between 0 and 66%. These variation is probably due to variable selection criteria and geographical differences. Late age of onset of DM, absence of neuropathy, absence of retinopathy, and presence of other systemic diseases are reported as markers of NDRD in different studies.

However, it remains unclear which clinical factors have greater value in the prediction of NDRD. As the reported incidence of NDRD in type 2 DM is high, it is necessary to predict, diagnose, and treat the concurrent glomerular diseases because of the prognostic and therapeutic importance. So far, only few such studies had been published from India. We carried out this study to find the clinical, laboratory, and pathological features of NDRD in type 2 DM patients and also to see any significant differences in clinical profile between the NDRD and DGS groups.

International: Uttara Das1, Kaligotla Venkata Dakshinamurty1, Aruna Prayaga2. Spectrum of IgA Nephropathy in a Single Center. Saudi J Kidney Dis Transpl 2015;26(5):1057-1063

Abstract

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common biopsy-proven primary glomerular disease in the world and a major contributor to the worldwide burden of endstage renal failure, with a wide geographical variation. To determine the incidence, clinical profile and histological pattern of IgAN in our institute, we reviewed all the patients who had native kidney biopsies with the diagnosis of primary IgAN during the period from 1998 to 2009 in the context of the clinical features. A total of 116 patients with IgAN were finally analyzed; 85 (73%) of the patients were male, the mean age of the patients was 29.2 ± 12.2 (range 10-70) years and the mean duration of disease was 10.4 ± 18.7 months (median: 2 months). Hypertension was present in 74 (63.2%) cases.

Gross hematuria was rare. The most common clinical presentation was nephrotic syndrome, followed by chronic renal failure. The mean proteinuria level was 2.5 ± 2.3 g/day (median: 1.7 g/day) and the mean serum creatinine level was 3.04 ± 3.3 mg/dL (median:1.7 mg/dL). The morphological sub-classification (Haas): Class I was the most common (44.4%), followed by class V (23%). IgA co-deposition with C3 and lambda was the most common finding in the immunofluorescence study. The glomerular filtration rate decreased with advanced histological damage. The incidence of IgAN was 7.5%, which is lower as compared with studies from elsewhere. IgAN in our population had a more severe clinical presentation.

Introduction

Primary immunoglobulin A (IgA) nephropathy (IGAN) is defined as the presence of IgAdominant glomerular deposition in the absence of systemic or other non-renal diseases. It is the most common biopsy-proven primary glomerular disease in the world.

There is a wide geographical variation existing around the globe, with incidence varying from 2-52%. In some countries such as Japan, China, Singapore, Hong Kong and Australia, the statistics show that nearly half of the biopsy-proven primary glomerular disease is IgAN. In the European countries, IgAN accounts for 10-20% of the total kidney biopsies. In the United States, this disease is common in certain areas. The incidence is dependent, to a large extent, on variations in the policies of renal biopsy among different countries.

Similarly, clinical features also vary from mild to severe forms. The most common presentations include synpharyngitic macroscopic hematuria, microscopic hematuria with proteinuria and hypertension and chronic renal failure. The relatively rare presentations include malignant hypertension, acute nephritic syndrome, acute renal failure and nephrotic syndrome.

Observations show high diversity on light microscopic features ranging widely from minimal histological lesions to severe diffuse proliferative lesions.

IgAN used to be considered benign in the classic descriptions. However, in India, it is not well characterized. Very few documented studies are available about this disease in India so far. Results from these studies prove that IgAN in India probably has a severe form of renal involvement.

The aim of our study was to estimate the incidence of IGAN in our institute and the spectrum of its clinical presentation besides the correlation with the histopathological classification.

International: Uttara Das, K. V. Dakshina Murty, Neela Prasad, Aruna Prayaga. Pulse Cyclophospamide in Severe Lupus Nephritis: Southern Indian Experience. Saudi J Kidney Dis Transpl.2010; 21(2): 372-378

Abstract

To evaluate the efficacy and safety of the monthly pulse IV cyclophosphamide (IVC) therapy in patients with severe lupus nephritis, we studied 39 patients of lupus nephritis on IVC therapy between 1998 to 2002. Single monthly cyclophosphamide (0.75-1 g/m²) was infused intravenously with oral prednisolone (0.5 mg/kg per day) and appropriate hydration. Of the 39 patients 25 (86.2%) patients were females and 4 (13.8%) were males. Six (2%) cases had irregular follow-up and 3 patients had expired during the initial cycles and were excluded from the study. The mean age was 25.6 + 6.72 years (range 10-40 years). The mean duration of the disease from the onset to renal biopsy was 24.2 + 18.5 months.

The clinical presentations included nephrotic syndrome (34.5%), acute glomerulonephritis (31.0%), Pyrexia of unknown origin (PUO) (10.3%), and rapidly progressive renal failure (6.7%). Renal insufficiency was present in 47.2% cases. Twenty-two (75.9%) patients had diffuse proliferative glomerulonephritis (class IV), 6 (20.7%) focal proliferative glomerulonephritis (class III), and one (3.4%) class Vd. After a mean follow-up of 15.8 months, out of 29 patients, 13 (44.8%) had achieved complete remission, 7 (24.1%) partial remission and 9 (31.0%) cases did not respond to the therapy. Side effects of the therapy included vomiting and nausea (100%) and hair loss during the first few doses of IVC. In addition, one case had dysfunctional uterine bleeding and two patients had avascular necrosis of femoral head. We conclude that our data indicate that IVC in severe lupus nephritis is effective in Indian patients though longer follow-up is required.

Introduction

Systemic lupus nephritis (SLE) is a multisystemic disease with a wide array of immunological abnormalities. Survival of patients with SLE have improved greatly, but lupus nephritis (LN) remains an important cause of morbidity and mortality. The aims of treating lupus nephritis are to induce and maintain remission thereby reducing the risk of progression to renal failure. Immunosuppressive drugs are more efficacious than prednisolone alone in controlling clinical signs of active nephritis, preventing renal scarring, and reducing the risk of end-stage renal disease (ESRD).

The most popular therapeutic regimen consists of long-term pulses IVC in combination with corticosteroid. However, some investigators have drawn attention to the limitation of IVC, including toxicity during long-term use and possibility of relapse. Despite skepticism, cyclophosphamide remains the most effective therapy for initial treatment for aggressive lupus nephritis. Several studies showed that neither pulse methyl prednisolone (MP) nor short course of pulse IVC are as efficacious as extended course of pulse cyclophosphamide in reducing the risk of renal progression or in achieving sustained remission of lupus nephritis

We aimed in this study to analyze our experiences and outcome of severe lupus nephritis treated with pulse cyclophosphamide and to evaluate risk factors for poor renal outcome.

Internatinal: Uttara Das, K.V. Dakshinamurty. Safety and Efficacy of Everolimus in Chronic Allograft Nephropathy. Saudi J Kidney Dis Transpl 2013;24(5):910-916.

Abstract

Chronic allograft nephropathy (CAN) is a major cause of late kidney allograft loss. Everolimus, a novel proliferation signal inhibitor, ameliorates CAN by its antiproliferative or apoptosis-enhancing effects. This study aims to evaluate the safety and efficacy of everolimus in renal transplant recipients with calcineurin inhibitor (CNI) withdrawal either due to CAN or cal-cineurin inhibitor toxicity (CNIT). A total 21 patients with CAN or CNIT converted from CNI to everolimus were prospectively studied from 2006 to 2009. There were 19 males and two females, with a mean age of 32.9 ± 10.7 years. Eight patients had chronic interstitial nephritis, three had diabetes mellitus, nine had end-stage renal disease and one had focal segmental glomerulosclerosis as native kidney disease. The mean duration of dialysis was 10.7 ± 7 months. 57.2% of the patients had CAN and 42.8% had CNIT.

Everolimus was started within six months of post-transplantation in six patients, within 6-12 months in two patients, within 1-2 years in four patients and after more than 2 years in nine patients. The mean dose at first month was 1.25 mg/day, at six month was 1.028 ± 0.3 mg/day and at 12 th month was 0.97 ± 0.2 mg/day, with a mean trough level of 6.35 ± 3 ng/dL, 5.18 ± 3 ng/dL and 6.43 ± 1.7 ng/dL, respectively. At the 12 th month, serum creatinine declined from 2.07 ± 0.58 mg/dL to 1.65 ± 0.81 mg/dL. The mean calculated glomerular filtration rate improved from 40.85 ± 8.8 mL/min to 56.84 ± 11.4 mL/min. No major side-effects were observed. Everolimus along with mycophenolate mofetil or azathioprine and prednisolone as a maintenance immunosuppressive therapy was found to be effective and safe in patients with CNIs withdrawal either due to CAN or CNIT.

Introduction

Chronic allograft dysfunction, which is also known as interstitial fibrosis/tubular atrophy (IF/TA) or chronic graft failure, is the second major cause of long-term graft failure. It is defined as functional and morphological deterioration of a renal allograft at least three to six months after transplantation. The incidence is about 2-3% per year. Despite advances in immunosuppressive therapy for control of acute allograft rejection, the long-term renal transplantation outcome had not significantly improved over the last decade. The causes of chronic allograft nephropathy (CAN) are multi-factorial. Calcineurin inhibitors (CNIs) have been a cornerstone of immunosuppression in solid organ transplantation since 1980, but have multiple side-effects including nephrotoxicity contributing to long-term allograft dysfunction.

Lowering the CNIs dose is associated with reduced nephrotoxicity. Calcineurin inhibitor toxicity (CNIT) is characterized by fibrotic changes throughout the kidney allograft and may contribute to CAN. Current immunosuppressive regimens do not adequately address the cause of long-term allograft dysfunction. Reducing dose or withdrawing CNIs along with control of blood pressure (BP), dyslipidemia and blood sugar and taking undue care during cold and warm ischemic periods may prevent the progression or occurrence of CAN. At present, the clinical challenge is to develop immunosuppressive protocols to decrease the risk of losing the graft in the long term, while keeping the current low-rates of biopsy-proven acute rejection (BPAR).

Several studies claim that newer immunosuppressive agents allow reducing or withdrawing CNIs without much effect on graft survival. Everolimus is a new proliferative signal inhibitor (PSI) that acts at a later stage of the cell cycle, blocking the proliferation signal provided by growth factors and preventing cells from entering the S phase. Several clinical studies had shown that everolimus has a multifactorial approach to improve the long-term outcomes by facilitating CNI minimization and inhibiting smooth muscle proliferation. We conducted this study to evaluate its efficacy and safety in CAN in our center.