[Show abstract][Hide abstract] ABSTRACT: Glomerular diseases are an important cause of chronic renal failure in developing countries. The spectrum of diseases causing nephrotic syndrome is changing globally in the last few decades. The aim of this prospective study was to look at this spectrum at a tertiary care center in North India and to analyze the changing trends over the last five decades. Patients in the age group 18-60 years with nephrotic syndrome were consecutively included in the study. Renal biopsies were performed in all patients and were subjected to light microscopy, immunofluorescence (IF) and electron microscopy (EM). While the IF was performed in 78% of cases, EM was available in one-fourth of cases. During 2002-2007, 364 patients (60.2% males) were included in the study. The mean age was 31.5 years. Primary glomerular diseases accounted for 89% of cases while lupus nephritis was the most common secondary glomerular disease. Focal segmental glomerulosclerosis (FSGS) accounted for 30.6% of primary glomerular diseases making it the most common cause of nephrotic syndrome. It was followed by membranous glomerulonephritis (MGN) in 24.4%, mesangiocapillary glomerulonephritis in 17.9% and minimal change disease in 14.8%. In the age group >40 years, MGN was the most common lesion (32.5%) followed by FSGS (27.7%). Over the last five decades, there was a nearly five-fold increase in the incidence of FSGS, 3-fold increase in MGN and a 10-fold reduction in diffuse proliferative glomerulonephritis while there was no major change in incidence of other diseases. The biopsy diagnosis of FSGS has increased considerably in last few decades and it is now the most common cause of nephrotic syndrome in adults in North India. MGN is the most common lesion in patients over 40 years of age.
Indian Journal of Nephrology 03/2014; 24(2):86-91.
[Show abstract][Hide abstract] ABSTRACT: Rheumatology Principles & Practice, a comprehensive rheumatology textbook, edited by Dr Ashit Syngle & Dr SD Deodhar . It brings together the academic and clinical experience of more than 60 contributors from across the world. It has been the brain child of Dr Ashit Syngle and the culmination of his three years labor of love. The highlights of the book are:
• It covers a range of topics within rheumatology and offers diagnostic and management options.
• It is comprehensively illustrated with original photos and contains algorithms and multiple choice questions.
• A unique interactive DVD supplements the book
It is an ideal book for graduate and post graduate medical students, interns, physicians, orthopaedicians, dermatologists, ophthalmologists, paediatricians, practitioners, physiotherapists, researchers and a valuable asset for libraries.
[Show abstract][Hide abstract] ABSTRACT: This study was designed to compare the outcomes of spousal donor (SD) with related donor (RD) kidney transplants performed at our center between January 2010 and October 2012. A total of 323 adult, ABO-compatible kidney transplants (SD 150 [46.4%], RD 173 [53.6%]) were included. Data on outcomes at 6 months post-transplant was collected retrospectively (2010-2011) and prospectively (January-October 2012). Majority of the donors (SD 88%, RD 72.2%) were females. In the SD group, donors were younger (SD 35.6 ± 8.2 years, RD 45.2 ± 11.5 years; P < 0.0001), whereas recipients were older (SD 42.2 ± 8.3 years, RD 30.0 ± 9.5 years; P < 0.0001). A significantly higher proportion of patients in the SD group were given induction therapy (43% vs 12%; P < 0.001). Biopsy proven acute rejections were more common in the RD group (16% vs 28.3%; P = 0.01). Majority (80.8%) of the acute rejections occurred in the first 2 weeks post-transplant in both groups. Isolated acute cellular rejections (ACRs) and isolated antibody mediated rejections constituted 50% and 25% of rejection episodes in both groups, whereas the remainder had histological evidence of both. The proportion of steroid responsive ACRs was similar in both groups (SD 83.3%, RD 65.4%; P = 0.2). The number of patients with abnormal graft function at the end of the study was higher in the RD group (2.3% vs. 12.3%; P = 0.001). Patient survival and infection rates were similar in the two groups. We conclude that short-term outcomes of SD transplants are not inferior to RD transplants. Lesser use of induction therapy in the RD group may explain the poorer outcomes as compared to the SD group.
[Show abstract][Hide abstract] ABSTRACT: Non-depleting antibody induction has the best safety profile in transplant recipients without an increased risk of infection or malignancy. This observational study was performed in intermediate immunologic risk live donor renal transplants to assess basiliximab efficacy in patients on tacrolimus, mycophenolate, and prednisolone immunosuppression. A total of 46 patients on basiliximab induction were compared to risk matched 56 controls at the end of 6 and 12 months post-transplant. An additional cost of approximately Rs. 100,000/patient was incurred by the basiliximab group. The incidence of biopsy proven acute rejection in the control group (12.5%, 6 months and 20.5%, 1 year) and the basiliximab group (13%, 6 months and 18.9%, 1 year) was similar. At 6 months, there was a non-significant trend toward more steroid sensitive rejections and better glomerular filtration rate preservation in the basiliximab group (83.3%, 71.9 ml/min) versus the control group (28.6%, 62.2 ml/min). However, this difference was lost at 1 year (70.1 ml/min vs. 67.6 ml/min). The incidence of infections was similar and none of the patients had a malignancy. Death censored graft survival (94.6% basiliximab and 94.8% control) and the mean number of hospitalizations for all reasons at the end of 1 year were not different among the two groups. In our study, basiliximab induction did not confer an additional advantage in the intermediate risk live donor transplants in patients on tacrolimus and mycophenolate based triple drug immunosuppression.
Indian Journal of Nephrology 11/2013; 23(6):409-12.
[Show abstract][Hide abstract] ABSTRACT: Monoclonal immunoglobulin deposition disease (MIDD) is an uncommon disease with a peak incidence between the 5(th) and 6(th) decades of life. It is characterized by non-fibrillar, Congo red negative deposition of monoclonal immunoglobulins in various organs, including in the kidneys. MIDD can be of three types depending on the composition of the deposits, and includes light chain deposition disease (LCDD), heavy chain deposition disease and light and heavy chain deposition disease, of which LCDD is the most common. Renal involvement is a universal finding in MIDD, and is in the form of renal insufficiency, microscopic hematuria and nephrotic range proteinuria. Gross hematuria is a rare occurrence. Renal biopsy usually shows nodular sclerosing glomerulopathy on light microscopy and diffuse linear staining of glomerular and tubular basement membrane on immunofluorescence microscopy. We report a young male who presented with rapidly progressive renal failure and gross hematuria and was diagnosed as LCDD with nodular glomerulopathy and crescents on renal biopsy.
Indian Journal of Nephrology 09/2013; 23(5):371-4.
[Show abstract][Hide abstract] ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication of organ transplantation. This study was a retrospective analysis of 2000 patients who underwent renal transplantation over a period of 30 years (1980-2010). Forty malignancies were diagnosed in 36 patients. Of these, 29 patients (1.45%) had PTLD (7 females, 22 males) accounting for 72.5% of all malignancies after transplantation. Twenty-two (75.8%) developed non-Hodgkin lymphoma and seven patients (24.2%) had myeloma. Diagnosis was made by biopsy of the involved organ in 21 patients (72.4%) and aspiration cytology in five patients (17.2%). In three patients, the diagnosis was made only at autopsy. Mean age at the time of diagnosis of PTLD was 41.9 years (range 21-69 years). Time interval from transplantation to the diagnosis of PTLD ranged from 3 months to 144 months with a median of 48 months. Only five patients (17.2%) developed PTLD within a year of transplantation. Twelve patients developed PTLD 1-5 years and 12 patients 5-10 years after transplantation. Organ involvement was extra nodal in 18 patients (82%). Thirteen (59%) patients had disseminated disease and nine (41%) had localized involvement of a single organ (brain-3, liver-1, allograft-1, perigraft node-1, retroperitoneal lymph nodes-3). Infiltration of the graft was noted in two patients. Patients with myeloma presented with backache, pathological fracture, unexplained anemia or graft dysfunction. PTLD was of B cell origin in 20 cases (70%). CD 20 staining was performed in 10 recent cases, of which 8 stained positive. Of the 26 patients diagnosed during life, 20 (69%) died within 1 year of diagnosis despite therapy. In conclusion, PTLD is encountered late after renal transplantation in the majority of our patients and is associated with a dismal outcome. The late onset in the majority of patients suggests that it is unlikely to be Epstein Barr virus related.
Indian Journal of Nephrology 07/2013; 23(4):287-91.
[Show abstract][Hide abstract] ABSTRACT: This study was carried out to evaluate the efficacy and safety of doxercalciferol as therapy for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 4 in a prospective clinical trial. A total of 35 CKD-4 patients who had a baseline parathyroid hormone (iPTH) >150 pg/mL and had not received any vitamin D analog in the preceding 8 weeks were followed up at intervals of 6 weeks for 18 weeks on oral therapy with doxercalciferol. The starting dose was 1.5 μg/day, and the dose was increased in steps of 1 μg/day if iPTH did not decrease by at least 30% on the subsequent visit. Doxercalciferol was stopped temporarily if low iPTH (<70 pg/mL), hypercalcemia (>10.7 mg/dL), or severe hyperphosphatemia (>8.0 mg/dL) occurred, and was restarted at a lower dose on reversal of these abnormalities. Calcium acetate was the only phosphate binder used. Mean iPTH decreased by 35.4 ± 4.4% from 381.7 ± 31.3 pg/mL to 237.9 ± 25.7 pg/mL (P < 0.001). The proportion of patients who achieved 30% and 50% suppression of iPTH levels was 83% and 72%, respectively. Mean serum calcium, phosphorus, and calcium-phosphorus product values did not differ significantly from the baseline values. Four, two, and nine patients developed hypercalcemia, severe hyperphosphatemia, and high CaxP (>55), respectively. Almost all patients recovered to an acceptable level within 2 weeks of stopping doxercalciferol and adjusting the phosphate binder dose. In all, 21 patients required temporary stoppage of therapy. Most of them were restarted on therapy at a reduced dose during the study. It can, therefore, be concluded that doxercalciferol is effective in controlling SHPT in CKD-4 patients with an acceptable risk of hyperphosphatemia and hypercalcemia.
Indian Journal of Nephrology 07/2013; 23(4):271-5.
[Show abstract][Hide abstract] ABSTRACT: Abnormalities in mineral and bone disease are common in chronic kidney disease (CKD). Evaluation of bone health requires measurement of parameters of bone turnover, mineralization, and volume. There are no data on bone health in CKD patients from India. In this cross-sectional study, we evaluated serum biomarkers of bone turnover: Bone-specific alkaline phosphatase (BAP) and total deoxypyridinoline (tDPD) along with parathyroid hormone, 25(OH) vitamin D, and bone mineral density (BMD) using dual absorption X-ray absorptiometry in a cohort of 74 treatment-naive patients with newly diagnosed stage 4 and 5 CKD (age 42 ± 14.5 years, 54 men) and 52 non-CKD volunteers (age 40.2 ± 9.3 years, 40 men). Compared to the controls, CKD subjects showed elevated intact PTH (iPTH), BAP, and tDPD and lower BMD. There was a strong correlation between iPTH and BAP (r = 0.88, P < 0.0001), iPTH and tDPD (r = 0.51, P < 0.0001), and BAP and tDPD (r = 0.46, P = 0.0004). The iPTH elevation was greater than twice the upper range of normal in 73% cases, and BAP was >40 U/L in 66% cases. The combination of these markers suggests high turnover bone disease in over 60% cases. The prevalence of osteopenia and osteoporosis was 37% and 12%, respectively. Osteoporotic subjects had higher iPTH, BAP, and tDPD, suggesting a role of high turnover in genesis of osteoporosis. Vitamin D deficiency was seen in 80%, and another 13% had insufficient levels. Vitamin D correlated inversely with BAP (r = -0.3, P = 0.009), and levels were lower in those with iPTH >300 pg/ml (P = 0.0.04). In conclusion, over 60% of newly diagnosed Indian stage 4-5 CKD patients show biochemical parameters consistent with high turnover bone disease. High turnover could contribute to the development of osteoporosis in CKD subjects. Deficiency of 25 (OH) vitamin D is widespread and seems to have a role in the genesis of renal bone disease. Studies on the effect of supplementation of native vitamin D are needed.
Indian Journal of Nephrology 05/2013; 23(3):161-7.
[Show abstract][Hide abstract] ABSTRACT: Spontaneous perirenal hematoma following ruptured microaneurysm is an unusual but serious complication of polyarteritis nodosa. We describe a young male who presented with spontaneous perirenal hematoma and was subsequently diagnosed to have polyarteritis nodosa. He was managed with immunosuppressive medications with no recurrence of symptoms.
Indian Journal of Nephrology 07/2012; 22(4):295-7.
[Show abstract][Hide abstract] ABSTRACT: Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Osteopontin (OPN) has been suggested to be associated with renal diseases characterized by tubulointerstitial fibrosis and proteinuria. However, information on association of genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic patients belonging to two independently ascertained cohorts using Real time PCR based Taqman assay. We observed a nearly threefold elevated risk of diabetic nephropathy among carriers of T allele and TT genotype of OPN C-443T polymorphism. Further, this allele was found to be significantly associated with proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our cohorts. This is the first study which suggests that OPN C-443T polymorphism may be a significant risk factor for diabetic nephropathy in type 2 diabetic patients.
Clinica chimica acta; international journal of clinical chemistry 05/2012; 413(19-20):1600-4. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a 26-year-old woman who was diagnosed eleven years ago with systemic lupus erythematosus and who had suffered multiple relapses. She presented with class IV lupus nephritis with thrombotic microangiopathy, for which she received three doses of rituximab along with plasmapheresis, with no response, and soon became dialysis dependent. One month after the last dose of rituximab, she presented with dyspnoea and hypoxia. A transbronchial lung biopsy revealed pulmonary fibrosis. A diagnosis of rituximab induced pulmonary fibrosis was made after excluding other causes and she was treated with intravenous methyl prednisolone with which there was marked improvement in symptoms and hypoxemia. This is the first report of rituximab induced pulmonary fibrosis in a patient with lupus nephritis.
[Show abstract][Hide abstract] ABSTRACT: Viral infections in renal allograft recipients constitute an important cause of renal graft dysfunction. They have shown an increasing incidence coinciding with more potent immunosuppression regimens. Cytomegalovirus (CMV) is well-known cause of a tubulointerstitial nephritis rich in plasma cells with cytopathic changes in tubular epithelial and endothelial cells. However, involvement of glomeruli and larger arteries in the absence of tubulointerstitial disease is rare. In this study, we demonstrated the spectrum of renal disease caused by CMV among renal allograft recipients. Retrospective analysis of 2900 renal allograft biopsies performed over a 10-year period revealed 10 cases of CMV infection, with half of them (5/10) detected in 2010-2011. Although tubulointerstitial nephritis due to CMV was the most common lesion (7/10), we noted an increased incidence of CMV glomerulopathy with (1/10) or without (3/10) coexisting tubulointerstitial CMV disease. Isolated glomerular involvement was characterized by a relative lack of inflammation in any of the compartments along with the presence of cytopathic changes in the glomerular endothelial cells and podocytes. Another patient had CMV-induced thrombotic microangiopathy. The coexistent diseases were calcineurin inhibitor toxicity (n = 1), antibody-mediated rejection (n = 1), cellular rejection (n = 2), and invasive fungal infection (n = 1). In conclusion, there is a wide spectrum of CMV-induced lesions. CMV glomerulopathy is characterized by cytopathic changes in glomerular endothelial cells and podocytes with a lack of significant inflammation. In contrast, CMV-induced arteriopathy can present as thrombotic microangiopathy. Coinfection with other pathogens like invasive fungi can lead to graft failure.
[Show abstract][Hide abstract] ABSTRACT: BK nephropathy (BKN) is an important complication of renal transplantation, with a reported incidence between 1% and 10% in different parts of the world. Known risk factors for the development of BKN are the recently introduced immunosuppressants and steroids. However, the preexisting viral load may add to the risk for development of BKN. Therefore, the present study was designed to monitor the baseline BK virus (BKV) DNA in renal transplant donors and recipients in India for correlation with the development of BKN.
This study used real-time polymerase chain reaction (PCR) for quantification of BKV DNA in the plasma of kidney transplant donors (n = 38) and recipients (n = 87) at the time of surgery. The control BKV DNA was manufactured from a known positive human sample, by cloning a 133-bp PCR product of bases 4,329 to 4,462 of the large T-antigen (TAg) of BKV in a plasmid vector.
Twenty-five of 87 recipient (28.7%) and 17/38 donor (44.7%) plasma samples were positive for BKV DNA at the time of transplantation with a median viral load of 910 (range 49-4770) and 312 (range 79-1508) copies per mL plasma, respectively. Six of 38 donor-recipient pairs showed viremia in both the recipient and donor: 1 developed histologically proven BKN at 18 months, 1 showed positive immunohistochemistry for SV40 TAg, and 2 others had high levels of viremia (14,545 copies at 6 and 2,617,524 copies at 3 months). None of the other 81 recipients showed evidence of BKN in the follow-up period.
This study showed that 28% of recipients and 44% of donors displayed baseline positivity for BKV DNA in plasma, which is higher than the reported incidence in the West. The baseline levels of BKV DNA in recipients with end-stage renal disease were higher than in donors. Dual positivity for BKV DNA in the plasma of donor-recipient pairs conferred a high risk of development of BK nephropathy in the allografted kidney.
[Show abstract][Hide abstract] ABSTRACT: Signaling through Toll-like receptor-9 (TLR9), a mediator of innate immune responses, could have a role in the pathogenesis of systemic lupus erythematosus (SLE). Some studies have shown an association between polymorphisms in the TLR9 gene and disease manifestations. We investigated whether two single nucleotide polymorphisms (-1486 T>C and +1174 G>A) in the TLR9 gene are associated with the risk of renal involvement in SLE. DNA samples from 112 SLE patients (62 with lupus nephritis) and 100 healthy controls were obtained. TLR9 polymorphisms (-1486 T>C and +1174 G>A) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allelic frequencies were compared between lupus patients and healthy controls. Clinical and laboratory manifestations and activity scores on renal biopsy of patients with lupus nephritis were compared between various genotypes. There was no difference in the frequency of genotype or allele distribution at either of the two loci between lupus patients and controls and in lupus patients with or without nephritis. Patients with CC/CT genotype at the -1486 position had higher serum creatinine (P = 0.03) and Austin activity scores (P = 0.015). Patients with AA/AG genotype at +1174 position showed higher serum creatinine (P = 0.04), proteinuria (P = 0.011), anti-dsDNA titers (P < 0.001) and Austin activity scores (P = 0.003) than the GG genotype. Variations at the -1486 and +1174 positions of TLR9 gene are not associated with increased risk of SLE or that of kidney involvement in North Indians. CC/CT genotypes at -1486 and AA/AG at +1174 positions are associated with more severe kidney disease at presentation.
Indian Journal of Nephrology 03/2012; 22(2):125-9.
[Show abstract][Hide abstract] ABSTRACT: The rare occurrence of human immunodeficiency virus (HIV) transmission through organ transplantation cannot override the huge impact that it has on the patient. We report a case of HIV transmission by renal transplantation in a 33-year-old housewife, who received a living related transplantation from her sister. Both the patient and her donor were negative by HIV antibody testing prior to transplantation, but were found to be infected in the ninth month after transplant. Further testing suggested that the donor was in the window period at the time of organ donation after having acquired the infection from her husband.
Indian Journal of Nephrology 03/2012; 22(2):133-5.
[Show abstract][Hide abstract] ABSTRACT: Diarrhea is common after kidney transplantation and is usually related to immunosuppressive medication or is infective in etiology. Inflammatory bowel disease (IBD) is rare after kidney transplantation and is unexpected because the patient is already immunosuppressed. Specific immunomodulatory actions of calcineurin inhibitors have been hypothesized to play a role in the development of IBD in such patients. We report a case of IBD developing de novo after kidney transplantation. Our case is unique in that the patient was not on calcineurin inhibitors for 8 years prior to the development of IBD.
Indian Journal of Nephrology 04/2011; 21(2):120-2.