Mycophenolate Mofetil with Steroid, a Reasonable Alternative to Current First-line Therapy, for Idiopathic Membranous Nephropathy in Resource-constrained Settings: A Randomized, Open-label Study.

BACKGROUND: The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile. Though mycophenolate mofetil (MMF) + steroid (S) is not recommended by Kidney Disease Improving Global Outcomes guidelines, it can be used as an alternative to mPR due to higher tolerability and steroid-sparing effect. Thus, we compared the safety and effectiveness of MMF + S and mPR regimens in patients with IMN. METHODS: This randomized, open-label study enrolled patients with adult-onset nephrotic syndrome (NS) and biopsy-proven IMN. Forty-two patients were allocated to MMF + S group (MMF 1 gm twice daily + oral prednisolone 0.5 mg/kg/day; n = 21) and mPR group [methylprednisolone (1 gm intravenous) for 3 days followed by alternating monthly cycles of oral prednisolone (0.5 mg/kg/day) for the next 27 days and cyclophosphamide (2 mg/kg/day) for 6 months; n = 21]. The primary outcome measure was change in urinary protein creatinine ratio (UPCR). RESULTS: At 6 months, both groups demonstrated a significant increase in serum albumin levels and estimated glomerular filtration rate (eGFR) (both p-values <0.0001) as well as a decrease in 24-hour proteinuria (MMF + S group: p-value = 0.003, and mPR group: p-value <0.0001) and UPCR (both p-values <0.0001). However, the groups did not differ in any of these parameters at any of the monthly follow-up visits. Moreover, the groups did not differ significantly in terms of the composite remission rates (61.91% for MMF + S group and 71.43% for mPR group). CONCLUSION: MMF + S and mPR had comparable tolerability and effectiveness, with MMF-associated advantage of reduced steroid exposure.

Rituximab treatment in resistant lupus nephritis: A single-center prospective study.

BACKGROUND: Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and failure to respond to traditional immunosuppression increases morbidity and mortality. Rituximab has been considered a novel therapeutic option for the management of SLE. MATERIALS AND METHODS: We conducted a single-center, prospective, observational study from July 2018 to June 2019 to evaluate the effectiveness of rituximab in patients with resistant LN. Resistant LN was defined as the failure to respond to conventional immunosuppressive therapy including both cyclophosphamide and mycophenolate mofetil. All adult patients (> 18 years) with biopsy-proven class III/IV LN were included in the study. Four doses of intravenous rituximab (375 mg/m2) on 0, 1, 2, 3 weeks were administered. Patients were followed for 6 months, and the rates of complete renal response (CRR), partial renal response (PRR), or no renal response (NRR) were measured. The change in baseline 24-hour urine protein, mean serum creatinine levels, and mean serum CD-19 levels at 24 weeks were also measured. RESULTS: Six months after rituximab therapy, total sustained renal response (CRR+PRR) was observed in 52% cases of resistant LN (CRR was achieved in 24% of patients and PRR in 28%, respectively). Rituximab was associated with a significant decline in the 24-hour urine protein, even in non-responders. However, the improvement in eGFR and serum creatinine was not statistically significant. The mean absolute CD-19 count was significantly low in responders compared to the non-responder group. CONCLUSION: Rituximab is a safe and effective therapeutic strategy for patients with resistant LN.

Idiopathic Nonlupus Full-House Nephropathy: Clinicopathological Presentation and Comparison with Lupus Full-House Nephropathy.

Full-house pattern on immunofluorescence (IF) on kidney biopsy in a patient without systemic lupus erythematosus is termed as nonlupus full-house nephropathy (FHN). In this study, we retrospectively compiled patients with nonlupus FHN and compared them with lupus FHN for clinicopathological presentation. We included patients with full-house IF patterns in renal biopsies collected from March 2007 to August 2018, clinical and histopathological data at the time of presentation were studied retrospectively. Treatment received and outcome at the end of follow-up was studied. Patients with nonlupus FHN who did not show any systemic disease (idiopathic group) were compared with a group of lupus nephritis patients. Of 178 patients, 34 had nonlupus FHN with 21 having idiopathic nonlupus FHN and 13 patients having secondary nonlupus FHN (membranous nephropathy, IgA nephropathy, postinfection glomerulonephritis). Males were more often in idiopathic nonlupus FHN patients than lupus FHN patients (P = 0.005). Kidney biopsies more often showed a mesangial (P = 0.0006) and less proliferative pattern of injury (P = 0.0002) and less intense C1q staining (P = 0.0001) in idiopathic nonlupus than lupus FHN. Clinically, idiopathic nonlupus FHN presented with more proteinuria (P = 0.0059) and less complement consumption (P = 0.001) than lupus FHN patients. Compared to lupus FHN, nonlupus has mainly nephrotic syndrome as clinical presentation. There was no difference in the clinical outcome between lupus FHN and idiopathic nonlupus FHN. Nonlupus FHN is not a very common condition and has less female involvement than in lupus FHN. Idiopathic nonlupus FHN has certain histopathological features with less C1q staining by IF, less frequent proliferative lesions and higher mesangial or membranous lesions by light microscopy compared to lupus FHN. Regarding outcomes, there is no significant difference between lupus FHN and idiopathic nonlupus FHN.

Characteristics, maternal and neonatal outcomes of acute kidney injury in preeclampsia: A prospective, single-center study.

BACKGROUND: Preeclampsia is an important cause of pregnancy-related acute kidney injury (AKI). The objective of our study was to determine the incidence, characteristics, and maternal and neonatal outcomes of AKI in pregnant women with preeclampsia. MATERIALS AND METHODS: A prospective, observational, single-center study from January 2019 to January 2020. Patients admitted with preeclampsia were included. Patients with obstetric complications were excluded. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. RESULTS: Total number of patients with preeclampsia was 104, out of which 25% developed AKI. Among those with AKI, nulliparity (61.5%) was the most common risk factor for preeclampsia followed by prior history of preeclampsia (15.4%), pregestational hypertension (11.5%), pregestational diabetes mellitus (3.8%), and chronic kidney disease (3.8%). There was no significant difference in maternal mortality between those with AKI (15.4%) and without AKI (7.7%). Intermittent hemodialysis was needed in 15.4%. At the end of 90 days follow-up, complete recovery of renal function occurred in 53.8%, partial recovery in 23.1% and end-stage kidney disease (ESKD) in 7.7%. Perinatal death occurred in 26.9%, preterm birth in 23.1% and stillbirth in 7.7% of those with AKI and was not significantly different from those without AKI. The mean of birth weight in newborns delivered by patients with AKI (2.53 ± 0.73 kg) was significantly lower compared to those without AKI (2.82 ± 0.58 kg). CONCLUSION: AKI was associated with a lower mean birth weight of newborns. Complete recovery of renal function was seen in 53.8% of patients with AKI and preeclampsia.

Histological patterns of renal diseases in children: A 12-year experience from a single Tertiary Care Center in North-East India.

This study was conducted to retrospectively investigate the indications for renal biopsy in the native kidneys of children and to analyze the pathological findings in a single tertiary care hospital in North-East India for the past 12 years. All children (≤18 years) who underwent renal biopsy at our hospital from March 2007 to April 2018 were included. Renal tissue specimens were studied under light and immunofluorescence microscopy. The study group included 254 patients (female 57%). The median age was 15 years (range 6-18 years). The most frequent indications for renal biopsy were nephrotic syndrome (NS) (53.9%), urinary abnormality in systemic disease (22.1%), nephritic syndrome (15.4%), asymptomatic hematuria (4.7%), significant proteinuria (3.1%), and unexplained renal failure (0.8%). On histopathological examination, primary glomerular diseases were the most frequent (68.9%) followed by secondary glomerular diseases (30.3%) and tubulointerstitial diseases (0.8%). The most common primary glomerular diseases were minimal change disease (26.8%), focal segmental glomerular sclerosis (12.2%), diffuse proliferative glomerulonephritis (9.1%), membranous nephropathy (8.7%), IgA nephropathy (8.3%), membranoproliferative glomerulonephritis (2%), and mesangioproliferative glomerulonephritis (2%). Lupus nephritis (LN) (29.5%) was the most common secondary glomerular disease. NS was the most common indication of renal biopsy, and LN was the most common histopathological diagnosis in children ≤18 years.

A Comparable Study on the Outcomes of Urgent Initiated Peritoneal Dialysis Versus Conventional Start, A Single Centre Study from North-East India.

INTRODUCTION: To avoid temporary hemodialysis, urgent initiated PD (UIPD) has been designed. In these patients, PD is initiated within 3 days after PD catheter placement. In this study, we evaluated the outcomes of UIPD in end-stage renal disease patients compared with the conventional start of PD. METHODS: This is a single-center observational study, comparing outcomes of UIPD to conventional initiation of PD. All patients diagnosed with ESRD from March 2013 to February 2019 and were willing for CAPD were recruited. In UIPD group treatment was initiated at day 2 of catheter insertion with a dialysate volume of 1000 mL per dwell for 2 hours gradually increased to 2000 mL per dwell volume by 8 to 10 days. RESULTS: During the study period, 98 patients were started on peritoneal dialysis in our hospital: 35 UIPD, 63 conventional PD. The mean age was 60.81 ± 13.04 years. 67% of patients were males with diabetes mellitus (32%) being the most common cause of CKD. Among the patients in UIPD, the mean age was 58.49 ± 16.1 years, while as in conventional group mean age was 62.10 ± 10.9 years. The Median follow-up time was 381 days. Technique survival was seen in 95 patients (96.9%). There was no difference in technique failure between UIPD vs conventional group. Total complications in our study occurred in 16 patients out of 98 patients during this period. There was no significant difference in the complication rates between the UIPD group and the conventional group. CONCLUSION: Our study showed that catheter patency, technique survival, and catheter-related complications were comparable between UIPD and conventional start peritoneal dialysis.

Prevalence of Nondiabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Clinicopathological Correlation: A Study from a Tertiary Care Center of Assam, India.

Diabetes mellitus is the most common cause of chronic kidney disease worldwide. The prevalence of nondiabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM) varies widely. This study aimed to evaluate the renal biopsies performed on type 2 diabetic patients for suspicion of NDRD and to correlate clinicopathological findings. All T2DM patients aged > 18 years were included in this study, who had renal biopsy performed for the following reasons: recent-onset nephrotic syndrome, unexplained rapid deterioration of renal function, proteinuria not accompanied by retinopathy, and unexplained hematuria. Renal biopsy was analyzed by light microscopy and immunofluorescence. Based on biopsy findings, the patients were grouped into three: (i) isolated NDRD, (ii) NDRD ± diabetic nephropathy (DN), and (iii) isolated DN. A total of 140 patients were enrolled in this study. Recent-onset nephrotic syndrome was the most common indication for biopsy, followed by the presence of active urine sediment. Forty-two percent of the patients had isolated DN, while NDRD was seen in 34% and DN ± NDRD in 24%. Focal segmental glomerulosclerosis (FSGS) and IgA nephropathy were the most common causes of isolated NDRD, while chronic tubulointerstitial nephritis (CTIN) was common in NDRD plus DN. Short duration of diabetes, absence of diabetic retinopathy, and lower glycated hemoglobin were predictive of NDRD. NDRD was seen in 58% of the patients with atypical presentations. FSGS and CTIN were common in NDRD diseases. Judicious use of biopsy in diabetic patients with atypical presentation may help in the diagnosis of NDRD.

Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury: A single-center retrospective study.

The aim of this study is to investigate the distinctive clinicopathological characteristics of acute kidney injury (AKI) in immunoglobulin A (IgA) nephropathy and identify the possible risk factors for AKI in IgA nephropathy. This study was a hospital-based retrospective analysis of clinicopthological data of IgA nephropathy. The study was conducted in the Department of Nephrology, Gauhati Medical College and Hospital, Assam, India from the period from January 2012 to December 2016. A total of 169 patients who met the inclusion or exclusion criteria were included in the study. Patient data (clinical/demographic and laboratory data including renal biopsy) were collected and were analyzed to assess the risk factors for AKI in IgA nephropathy. For the purpose of analyses, the patients were divided into two groups, AKI (n = 28) and non-AKI group (n = 141). Twenty-eight patients out of 169 developed AKI. The prevalence of AKI in IgA nephropathy patients in our center was 16.5% (28/169). Most AKI patients were hypertensive, hyperlipidemic, had pre-existing impaired kidney function, and higher baseline serum creatinine, higher serum uric acid, and proteinuria, with lower serum albumin and hemoglobin (P <0.05). Use of herbal medications was also significantly more common in the AKI group (P <0.003). Pathological features, like crescents (both cellular and fibrocellular) and interstitial fibrosis/tubular atrophy, were also more severe in the AKI group (P <0.003). In multivariate logistic regression analysis, we found that hypertension, proteinuria, cellular and fibro-cellular crescents, glomerular sclerosis were possible risk factors for AKI. Prevalence of AKI in IgA nephropathy is not as uncommon in north-eastern India as previously thought and knowledge of risk factors for AKI can help in early identification of individuals at risk.

Clinical and histopathological profile of lupus nephritis and response to treatment with cyclophosphamide: A single center study.

Lupus nephritis (LN) is an immune-complex glomerulonephritis that is usually manifested by proteinuria, active urinary sediment, hypertension, and renal failure. The objective of this study is to study the clinical and histopathological profile of LN and the response to treatment with cyclophosphamide. This was a retrospective study conducted in a tertiary care center in Assam, India, where 176 LN patients who underwent renal biopsy were included. The presenting features, laboratory parameters such as proteinuria, hematuria, and the histopathological class of the patients were studied. Among the 176 patients, 89.8% were female and 10.2% were male and maximum patients (61.3%) were in the age group of 20-40 years. Pedal edema was present in 100% of the patients, decreased urine output in 43.7%, malar rash in 38%, joint pain in 42%, hair loss in 63%, hypertension in 41.4%, oral ulcers in 31.8%, seizures in 17%, psychosis in 13%, hematuriain 78.4%, anemia in 72.1%, thrombocytopenia in 51.1%, and leukopenia in 31.7% of patients. The anti-nuclear antibody was positive in all patients and anti-dsDNA was positive in 70.5% of the patients. The most common histopathological type was class IV (50%), followed by class III (17.6%). One hundred and two patients received intravenous cyclophosphamide as initial treatment of whom, 40 received the Eurolupus regimen and 62 received the NIH regimen. The number of patients who underwent remission in both the regimen was compared. The response rate of initial treatment with cyclophosphamide in the Eurolupus group was 62.5% and in the NIH group was 64.5% (P >0.05). Majority of the patients had proliferative LN in this study, of which class IV was the most common. Proliferative LN, if not detected and treated early, leads to poor outcome in terms of patient and renal survival. Hence, patients with systemic lupus erythematosus should be evaluated for kidney involvement and treated accordingly for better outcome.

Acute kidney injury in children with nephrotic syndrome: a single-center study.

BACKGROUND: Children with nephrotic syndrome (NS) are at risk for the development of acute kidney injury (AKI) through a variety of mechanisms.The frequency of NS hospitalizations complicated by AKI has almost doubled in the last decade. Children with AKI have longer hospital length of stay and increased need for intensive care unit admission. The main objectives of this study were to determine the incidence, clinical characteristics, risk factors and short-term outcome of AKI in children hospitalized with NS. METHODS: In this retrospective study, 355 children ≤18 years of age with a clinical diagnosis of NS admitted in the Department of Nephrology, Gauhati Medical College and Hospital from January 2012 to December 2015 were reviewed. RESULTS: The incidence of AKI in children with NS was found to be 23.66%, 11.24%, 7.95% and 4.48% of children entered Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) Stages R, I and F, respectively. Infection {odds ratio [OR] 2.53 [95% confidence interval (CI) 1.52-4.22]} and nephrotoxic medication exposure [OR 7.8 (95% CI 4.06-15.01)] were common factors associated with AKI. Children with steroid-dependent NS (SDNS) and steroid-resistant NS (SRNS) were more likely to develop AKI compared with children with steroid-sensitive NS (SSNS). The mean time to recovery for groups pRIFLE Stages R, I and F were 15 ± 2 , 22 ± 3 and 28 ± 5 days, respectively. Children with NS who were hypertensive, had higher urinary protein excretion and low serum albumin were more prone to develop AKI. CONCLUSIONS: AKI is not uncommon in children with NS. Infection and exposure to nephrotoxic drugs are common factors associated with AKI. AKI is more frequent in SDNS and SRNS compared with SSNS. The mean time to recovery is prolonged with more severe AKI.

Etiological profile of chronic kidney disease: A single-center retrospective hospital-based study.

Chronic kidney disease (CKD) is one of the leading causes of chronic diseases globally, with rising incidence and prevalence. It is a major risk factor for cerebrovascular disease and coronary artery disease, which are the main causes of death in this population. The etiology of CKD is varied. This study was performed to evaluate the various etiologies of CKD among patients presenting to the Department of Nephrology, Guwahati Medical College, a tertiary referral center. A total of 5718 CKD patients were evaluated to identify the cause of CKD. The most common cause was found to be diabetes mellitus in 42.2%, followed by chronic glomerulonephritis in 21.4%, hypertension in 19.5%, obstructive uropathy in 6.9%, chronic interstitial nephritis in 3.6%, and autosomal dominant polycystic kidney disease in 1.5% of the patients. Nearly 2.7% of the patients had CKD of unknown etiology. Most of the common causes of CKD are potentially treatable and initiating appropriate treatment early may prevent the development of CKD or progression to end-stage renal disease.

Nephrogenic systemic fibrosis: an emerging entity.

Nephrogenic systemic fibrosis (NSF) is a progressive disorder which has been seen only in patients with chronic kidney disease. It is associated with fibrosis of the skin and connective tissue throughout the body. The skin thickens and becomes hard, rigid, and coarse, which severely restricts movement of the joints. It can also lead to widespread fibrosis of internal organs involving lungs, heart, diaphragm, esophagus, and skeletal muscle, and in some cases may lead to death. Based on case series reports and skin biopsy showing gadolinium (Gd) ions, NSF has been directly linked to Gd contrast exposure given during MRI/MRA. There are over 250 reported cases of NSF worldwide with hundreds still not reported or remaining undiagnosed. Symptoms of NSF appear within 2-75 days, with a mean of 25 days after exposure to Gd contrast. This disorder is not well understood, and more research is needed to obtain information about how Gd causes this condition. Currently there is no effective treatment, so prevention is the only way to avoid this serious illness.