[Show abstract][Hide abstract] ABSTRACT: No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 μmol/l, and neurological or pulmonary lupus were excluded. MMF was prescribed at daily doses of 1.5-3 g for 24 weeks, while CYC was administered as six fortnightly infusions of 500 mg each. All patients received three methylprednisolone injections, followed by oral corticosteroids. Maintenance therapy with azathioprine and low-dose corticosteroid was started at end of induction therapy. The primary end point was treatment response at 24 weeks, while secondary end points were complete remission, Systemic Lupus Erythematosus Disease Activity Index and adverse events. Of the 173 patients recruited, 100 were equally randomized to receive either CYC or MMF. Baseline characteristics were similar, except for higher 24 h proteinuria in the CYC group. At 24 weeks, 37 patients in each group achieved the primary end point. The complete remission rate was 50% in CYC and 54% in MMF group. Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.Kidney International advance online publication, 21 October 2015; doi:10.1038/ki.2015.318.
Kidney International 10/2015; DOI:10.1038/ki.2015.318 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Steroids are used in the management of drug-induced acute interstitial nephritis (AIN). The present study was undertaken to compare the efficacy of pulse methyl prednisolone with oral prednisolone in the treatment of drug-induced AIN. Patients with biopsy-proven AIN with a history of drug intake were randomized to oral prednisolone (Group 1) 1 mg/kg for 3 weeks or a pulse methyl prednisolone (Group II) 30 mg/kg for 3 days followed by oral prednisolone 1 mg/kg for 2 weeks, tapered over 3 weeks. Kidney biopsy scoring was done for interstitial edema, infiltration and tubular damage. The response was reported as complete remission (CR) (improvement in estimated glomerular filtration rate [eGFR] to ≥60 ml/min/1.73 m 2 ), partial remission (PR) (improvement but eGFR <60 ml/min/1.73 m 2 ) or resistance (no CR/PR). A total of 29 patients, Group I: 16 and Group II: 13 were studied. Offending drugs included nonsteroidal anti-inflammatory drugs, herbal drugs, antibiotics, diuretic, rifampicin and omeprazole. There was no difference in the baseline parameters between the two groups. The biopsy score in Groups I and II was 5.9 1.1 and 5.1 1.2, respectively. At 3 months in Group I, eight patients each (50%) achieved CR and PR. In Group II, 8 (61%) achieved CR and 5 (39%) PR. This was not significantly different. Percentage fall in serum creatinine at 1 week (56%) was higher in CR as compared to (42%) those with PR. ( P = 0.14). Patients with neutrophil infiltration had higher CR compared to patients with no neutrophil infiltration ( P = 0.01). Early steroid therapy, both oral and pulse steroid, is equally effective in achieving remission in drug-induced AIN.
Indian Journal of Nephrology 09/2015; 25(5):281. DOI:10.4103/0971-4065.147766
[Show abstract][Hide abstract] ABSTRACT: Aim:
A significant proportion of pauci-immune glomerulonephritis (PIGN) patients are reported to have absence of anti-neutrophilic cytoplasmic antibodies (ANCA). However, studies are controversial regarding their significance and there is limited data after the new prognostic classification of PIGN.
Renal biopsy-proven cases of PIGN were included and their clinical details, ANCA status by immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), Birmingham Vasculitis Activity Score (BVAS) and treatment outcomes at 6 months were noted. The renal biopsies were classified according to the proposed histopathological classification. Scoring was done from 0-3 for interstitial edema, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and arteriosclerosis. The percentage of glomeruli with sclerosis, cellular and fibrous crescents, and percentage of subjects with glomerulitis, tuft necrosis, interstitial granuloma and vasculitis were noted.
Out of the 84 subjects included in the study, 33 (39.3%) were negative for ANCA by both IIF and ELISA. These subjects had significantly higher renal involvement, less extra-renal manifestations and lower BVAS. On histology, they had significantly higher proportion of crescentic class (66.7% vs. 41.2%, P = 0.039), higher number of cellular crescents (66.12% vs. 53.3%, P = 0.00008), higher IFTA (1.53 vs. 1.02, P = 0.009) and less interstitial edema (1.44 vs. 1.96, P = 0.003). The treatment outcomes were worse in ANCA-negative PIGN subjects, with significantly less improvement (37.2% vs. 62.8%, P = 0.02), more deterioration (40.7% vs. 14%, P = 0.006), and reduced probability of becoming dialysis free (31.6% vs. 69.6% P = 0.009).
A negative ANCA in PIGN is associated with crescentic class, more IFTA and poor treatment outcomes.
International Journal of Rheumatic Diseases 08/2015; DOI:10.1111/1756-185X.12729 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsImmunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome.Methods
This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4TIN followed for a minimum period of 1 year or until end-stage renal disease.ResultsIgG4TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up.Conclusion
IgG4TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease.
International Journal of Rheumatic Diseases 08/2015; DOI:10.1111/1756-185X.12675 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There have been very few studies comparing cyclophosphamide (CTX) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy (NIST) resistant idiopathic membranous nephropathy (IMN). The present study was aimed at comparing the efficacy and safety of tacrolimus (TAC)/steroids with cyclical CTX/steroids (Modified Ponticelli regimen (MPR)) in patients with IMN.
IMN patients (n=70) with persistant nephrotic syndrome after atleast 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally randomized to receive TAC with oral prednisolone (TAC*) or MPR. Antibodies against m-type phospholipase A2 receptor (PLA2 R Ab) were tested for at baseline and, at 6 and 12 months after start of therapy. The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups.
Intention-to-treat analysis showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; p=0.30) and 12 months (71% with TAC* vs. 77% with MPR; p=0.78) were comparable. PLA2 R Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum albumin (r -0.49/-0.53) at the end of therapy. Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity.
In NIST refractory IMN, both TAC* and MPR are comparable, but with different adverse effect profile. PLA2 R Ab has a very good association with proteinuria, and should be regularly monitored on clinical follow-up.
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[Show abstract][Hide abstract] ABSTRACT: To evaluate sequential changes in biochemical bone parameters, parathyroid hormone (iPTH), vitamin D levels and bone mineral density (BMD) over a period of 24 weeks after renal transplantation, we studied 75 patients (58 males, with a mean age of 35.4 years) who underwent their first renal transplantation without a past history of parathyroid surgery or fractures. Serum calcium, phosphorus and albumin were measured before transplant, then weekly for four weeks and monthly for the following 20 weeks. Serum iPTH and vitamin D levels and BMD were measured at baseline and 24 weeks after transplantation. After transplantation, there was a significant fall in serum calcium in the first week, followed by a gradual rise. At 12 and 24 weeks, respectively, 17.5% and 8% patients had hypercalcemia. Serum phosphorus decreased after transplant and at 24 weeks; 25% patients had hypophosphatemia. The iPTH levels declined significantly from 251 ± 218.2 pg/mL before transplant to 97 ± 142.8 pg/mL at the end of the study period. At 12 and 24 weeks, 42.7% and 51.3% patients, respectively, had persistent hyperparathyroidism (HPT). Elevated baseline iPTH levels and graft dysfunction were the risk factors for HPT at 12 weeks, while low vitamin D levels were the risk factor at 24 weeks. The BMD showed a significant decline of 2.7% after transplant, and it negatively correlated with the pre-transplant iPTH levels; the patients who received tacrolimus immunosuppression had a lower decline in BMD than the rest of the patients. No fractures were reported during the study period. We conclude that, after renal transplantation, hypercalcemia and hypophosphatemia are common, while a significant proportion of patients have persistent HPT and decline in bone mineral density.
Saudi journal of kidney diseases and transplantation: an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 07/2015; 26(4):671-677. DOI:10.4103/1319-2442.160127
[Show abstract][Hide abstract] ABSTRACT: Osteopontin (OPN) C-443T promoter polymorphism has been shown as a genetic risk factor for diabetic nephropathy (DN) in type 2 diabetic patients (T2D).
In the present study we investigated the association of three functional promoter gene polymorphisms C-443T, delG-156G, and G-66T and their haplotypes with the risk of DN and estimated Glomerular Filtration Rate (eGFR) in Asian Indians T2D patients using Real time PCR based Taqman assay. A total of 1165 T2D patients, belonging to two independently ascertained Indian Asian cohorts, were genotyped for three OPN promoter polymorphisms C-443T (rs11730582), delG-156G (rs17524488) and G-66T (rs28357094).
-156G allele and GG genotypes (delG-156G) and haplotypes G-C-G and T-C-G (G-66T, C-443T, delG-156G) were associated with decreased risk of DN and higher eGFR. Haplotype G-T-delG and T-T-delG (G-66T, C-443T, delG-156G) were identified as risk haplotypes, as shown by lower eGFR.
This is the first study to report an association of OPN promoter gene polymorphisms; G-66T and delG-156G and their haplotypes with DN in T2D. Our results suggest an association between OPN promoter gene polymorphisms and their haplotypes with DN.
Journal of Clinical Medicine 06/2015; 2015(4):1281-1292. DOI:10.3390/jcm4061281
[Show abstract][Hide abstract] ABSTRACT: Current management guidelines for lupus nephritis (LN) do not attach importance to histological indices of disease activity or chronicity. The present study was performed to evaluate the clinical relevance of these indices in determining outcomes in patients with class IV LN. We analyzed the data of all patients with biopsy-proven class IV LN seen over a 6-year period. The histopathological findings were reviewed; the activity and chronicity indices proposed by Austin [AI (Austin) & CI (Austin)] and the renal biopsy index proposed by Hill were calculated. As immunofluorescence was not done in all patients, this was excluded from calculation of the renal biopsy index, which was referred to as the modified Hill's index (MHI), which was a composite of glomerular activity index (GAI), chronicity index (CI) and tubulo-interstitial activity index (TIAI). Pearson's correlation coefficient, multilinear regression analysis and logistic analysis were performed, and p value of <.05 was considered significant. During the study period, 114 cases of LN were evaluated, of which 64 % (73/114) had class IV LN. The mean age was 26.5 years, and 92 % were females. The mean scores of AI (Austin), CI (Austin), GAI, CI, TIAI and MHI were 8.46, 2.50, 7.54, 3.06, 4.74 and 2.23, respectively. Serum creatinine correlated significantly with TIAI, CI, CI (Austin) as well as MHI, but not with AI (Austin) or GAI. The serum creatinine level was the strongest clinical parameter determining outcome, while none of the histological indices correlated with either treatment outcome or mortality. None of the histological indices performed better than serum creatinine level in determining the treatment outcomes and mortality.
Rheumatology International 03/2015; 35(9). DOI:10.1007/s00296-015-3240-2 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a 50-year-old female who presented with inflammatory arthritis, upper respiratory tract symptoms, and microscopic hematuria with nephrotic range proteinuria. Antineutrophil cytoplasmic antibodies (ANCA) were detectable and kidney biopsy showed pauci-immune focal necrotizing crescentic glomerulonephritis. She was treated with pulse intravenous cyclophosphamide (CYC) and prednisolone. Patient developed severe leucopenia after the first dose and subsequently had leucopenia to low dose CYC, mycophenolate mofetil and azathioprine were also tried. However, patient developed leukopenia with all the above agents. Initiation of tacrolimus (TAC) was followed by dramatic response: Proteinuria decreased, serum albumin normalized and C-ANCA and anti-PR3 ANCA assays became negative. This is the first successful case of TAC as an induction agent in a patient with GPA (ANCA associated vasculitis with renal involvement).
Indian Journal of Nephrology 02/2015; 25(1):46. DOI:10.4103/0971-4065.136885
[Show abstract][Hide abstract] ABSTRACT: A 60-year male was admitted with advanced renal failure and bilaterally enlarged kidneys. Kidney biopsy revealed diffuse interstitial infiltration by CD20 + lymphomatous cells suggestive of diffuse large B-cell, non-Hodgkin's lymphoma. Bone marrow examination was negative for malignant cells. Positron emission tomography-computed tomography showed uniformly diffuse and avid flurodeoxy glucose uptake in both kidneys, multiple hypodense areas of both lobes of liver, and axial and appendicular skeleton. Patient was treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone, became afebrile and serum creatinine normalized.
Indian Journal of Nephrology 02/2015; 25(1):43-5. DOI:10.4103/0971-4065.140723
[Show abstract][Hide abstract] ABSTRACT: Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen) is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA) axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 μg) was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2%) had low basal cortisol levels, only 3 (23%) had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.
Indian Journal of Nephrology 02/2015; 25(1):12. DOI:10.4103/0971-4065.136884
[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus is a common cause of pyelonephritis. Both emphysematous pyelonephritis (EPN) and non-EPN (NEPN) are associated with poor outcome. This study was aimed at analyzing the clinical features, microbiological profile, prognostic factors, and treatment outcome of pyelonephritis in diabetic patients. A total of 105 diabetic patients with pyelonephritis were admitted from July 2010 to June 2012. Patients were treated with appropriate antibiotics and percutaneous drainage (PCD) as indicated. Nephrectomy was carried out in patients of EPN who were refractory to conservative measures. NEPN and EPN were seen in 79 (75.2%) and 26 (24.7%) patients, respectively. Escherichia coli was the most common organism. Pyelonephritis was associated with renal abscess and papillary necrosis in 13 (12.4%) and 4 (3.8%) patients with EPN and NEPN, respectively. Worsening of renal functions were seen in 92 and 93% of patients with EPN and NEPN, respectively. Class 1 EPN was seen in 2 (7.7%), Class II in 8 (30.7%), IIIa in 7 (27%), IIIb in 5 (19.3), and IV in 4 (15.4%) patients. Antibiotics alone were sufficient in 38.5% of EPN versus 62% in NEPN; additional PCD was required in 42.3% in EPN and 21.4% in NEPN. Nephrectomy was required in 5 (19.2%) EPN patients with Class IIIB or IV. A total of 13 patients (12.4%) expired, 4 (15.4%) in EPN, and 9 (11.4%) in NEPN group. Patients with EPN had a higher incidence of shock (6% vs. 0; P < 0.05) and poorly controlled blood sugar (26% vs. 50%; P < 0.05) compared with NEPN. Presence of shock and altered sensorium were associated with poor outcome in patients with EPN. Diabetics with pyelonephritis have severe disease. Patients of EPN have poorer treatment outcome compared with those with NEPN. However, there is no difference in the mortality, but a greater need of nephrectomy in EPN compared with NEPN patients. Presence of shock and altered sensorium at presentation were poor prognostic factors in EPN.
Indian Journal of Nephrology 12/2014; 24(6):367-371. DOI:10.4103/0971-4065.135347
[Show abstract][Hide abstract] ABSTRACT: Rapidly progressive renal failure is a common but severe feature of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A histopathological classification for ANCA-associated pauci-immune glomerulonephritis was developed for prognostication of these patients. The present study aims to classify patients of pauci-immune glomerulonephritis according to this classification and its impact on outcome. Eighty-six subjects with pauci-immune glomerulonephritis between July 2006 and October 2012 were included in the study. Their renal biopsies were reviewed and classified into focal, crescentic, sclerotic and mixed class as per the new classification. The outcomes were analyzed after 6 months of treatment. Of the 86 subjects, 34 (39.53 %) were granulomatosis with polyangiitis, 36 (41.86 %) microscopic polyangiitis, 1 eosinophilic granulomatosis with polyangiitis, while the rest (17.44 %) were unclassifiable. Thirteen (15.5 %), 43 (51.2 %), 12 (14.3 %) and 16 (19 %) patients were classified as focal, crescentic, sclerotic and mixed class, respectively. The mean serum creatinine at baseline was 280.23, 659.46, 573.72 and 542.78 µmol/L in focal, crescentic, sclerotic and mixed class, respectively. The probability of improvement in renal functions at 6 months decreased from focal to crescentic to mixed to sclerotic class, while the probability of death was highest in the sclerotic class followed by the mixed class. This difference in outcome was maintained irrespective of the clinical diagnosis or the Birmingham Vasculitis Activity Score. Our study has shown that the histopathological classification can be used to predict the severity of renal dysfunction as well as the treatment outcomes in pauci-immune glomerulonephritis.
Rheumatology International 11/2014; 34(12):1721-7. DOI:10.1007/s00296-014-3041-z · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Renal transplant recipients are at high risk of developing multiple infections, often concomitantly because of their immunocompromised status. Post renal transplant infections are often elusive and require extensive evaluation for proper diagnosis and treatment. A high index of suspicion is required and an attempt should be made to confirm the microbiological diagnosis from each site involved to rule out multiple infections.
We report a 50-year-old female, a renal allograft recipient who presented with left hemiplegia, esophageal ulcers and fever 3 months after her transplant. Esophageal biopsy revealed Cytomegalovirus (CMV) inclusions and the whole blood quantitative CMV polymerase chain reaction (PCR) was positive. Neuroimaging showed a brain abscess, stereotactic biopsy from which revealed Scedosporium apiospermum on fungal culture. Her tacrolimus and mycophenolate were stopped and she was managed with intravenous ganciclovir and voriconazole. With these measures, she showed marked improvement in her general and neurological condition. Two months later, she developed recurrence of fever with dry cough. Radiological investigation revealed a cavitating lung lesion, a needle aspiration from which demonstrated acid-fast bacilli. She was started on antituberculous treatment. With these measures, she recovered completely and maintained good graft function despite being on only prednisolone 10 mg once a day.
Although CMV disease is not uncommon in the first three months post transplant, Scedosporium is a rare cause of brain abscess. On the other hand, tuberculosis is common in transplant recipients, especially in developing countries, like India. However, this is the first case report of occurrence of these three infections in the same patient, demonstrating the importance of a good microbiological work-up from each site involved in immunosuppressed subjects.