Clinico-Epidemiological Profile of Patients with Chronic Kidney Diseases of Unknown Etiology: A Hospital-Based, Cross-Sectional Study from Central India.

Background: Chronic kidney disease (CKD) not associated with known risk factors, called CKD of unknown etiology (CKDu), has been reported from several geographically distinct regions across the world. This study reports the clinical and epidemiological profile of patients with CKDu from a new hotspot in central India. Materials and Methods: This cross-sectional study describes the sociodemographic, clinical, and laboratory profile of the patients diagnosed with CKDu visiting a tertiary care public hospital in the state of Chhattisgarh in central India between June 2019 and June 2021. CKDu was diagnosed as progressive CKD, minimal proteinuria, absence of hematuria, diabetes, severe hypertension, systemic illness, glomerulonephritis or other urinary tract diseases, and presence of symmetrically contracted kidneyon ultrasound. Results: A total of 166 (3.1%) out of 5365 patients with CKD were diagnosed with CKDu. The mean age was 53.6 ± 11.8 years. The patients were predominantly male (n = 113, 68.1%), belonged to rural areas (n = 147, 88.6%), and were engaged in farming (n = 105, 63.3%). The estimated glomerular filtration rate (eGFR) at presentation was 21.5 ± 15.1 ml/min/1.73m2. Forty-four (26.5%) had stage 3 CKD, 57 (34.3%) had stage 4 CKD, and 65 (39.2%) had stage5 CKD. There was an over-representation of CKDu cases in patients with CKD from Gariyaband (36.0%) and Mahasamund (25%) districts of Chhattisgarh and Nuapada (35.0%) and Balangir (30.0%) districts of Odisha. Conclusion: The study suggests clustering of cases of CKDu in certain districts of Orissa and Chhattisgarh.

Prevalence and associated factors of impaired kidney functions among children and adolescents in India: insights from the Comprehensive National Nutrition Survey (CNNS) 2016-18.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health problem. The burden of CKD in children and adolescents in India is not well described. We used data from the recent Comprehensive National Nutrition Survey (CNNS) to estimate the prevalence of impaired kidney function (IKF) and its determinants in children and adolescents between the ages of 5 and 19. METHODS: CNNS 2016-18 adopted a multi-stage sampling design using probability proportional to size sampling procedure after geographical stratification of urban and rural areas. Serum creatinine was tested once in 24,690 children and adolescents aged 5-19 years. The estimated glomerular filtration rate (eGFR) was derived using the revised Schwartz equation. The eGFR value below 60 ml/min/1.73 m2 is defined as IKF. Bivariate analysis was done to depict the weighted prevalence, and multivariable logistic regression examined the predictors of IKF. RESULTS: The mean eGFR in the study population was 113.3 + 41.4 mL/min/1.73 m2. The overall prevalence of IKF was 4.9%. The prevalence in the 5-9, 10-14, and 15-19 year age groups was 5.6%, 3.4% and 5.2%, respectively. Regression analysis showed age, rural residence, non-reserved social caste, less educated mothers, Islam religion, children with severe stunting or being overweight/obese, and residence in Southern India to be predictors of IKF. CONCLUSIONS: The prevalence of IKF among children and adolescents in India is high compared to available global estimates. In the absence of repeated eGFR-based estimates, these nationally representative estimates are intriguing and call for further assessment of socio-demographic disparities, genetics, and risk behaviours to have better clinical insights and public health preparedness.

The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics.

BACKGROUND: Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low-middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. METHODS: ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. RESULTS: A total of 4056 patients have been enrolled up to 31 March 2020. The mean ± SD age was 50.3 ± 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73 m2. About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. CONCLUSIONS: The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.

Immunosuppressive Therapy in Primary Membranous Nephropathy with Compromised Renal Function.

INTRODUCTION: Renal dysfunction at presentation is uncommon in primary membranous nephropathy (PMN). The data on the outcome of PMN patients with renal dysfunction at outset are scarce. The objective of the current study was to report the clinical outcomes of PMN patients with renal dysfunction. MATERIAL AND METHODS: This prospective longitudinal observational study included PMN patients (both incident and treatment resistant) with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. Immunosuppressive treatment was as per the unit's protocol. Patients were evaluated for proteinuria, creatinine, and serum albumin at monthly intervals for 6 months, then quarterly for a year, and then biannually. Both serum and tissue anti-PLA2R were performed at baseline. OUTCOME: Percentage of patients achieving clinical remission. RESULTS: Sixty-four adults met study criteria and were analysed. The median (IQR) age of the patients was 48 (40, 56) years. PMN was PLA2R related in 52 (81.3%) patients. Twenty-eight (43.8%) and 30 (46.9%) patients were in remission at 12 months and at the end of the study [median (IQR) follow up: 24 months (12, 35)], respectively. Eight (12.5%) had progressed to end-stage renal disease at the last follow-up. Median (IQR) baseline anti-PLA2R titre was 150.1 RU/mL (38.5, 308). Nineteen (61.3%) and 18 (58.1%) patients with >90% reduction in anti-PLA2R titres at 12 months were in clinical remission at 12 months and at the end of the follow-up, respectively. Both cyclical cyclophosphamide/steroids (cCYC/GC) and rituximab were equally effective in inducing remission, but rituximab had a favourable adverse event profile compared to cCYC/GC. CONCLUSION: To conclude, both cCYC/GC and rituximab are equally effective in inducing remission of nephrotic state with compromised renal function due to PMN. Immunosuppression induces remission in up to 50% PMN patients with CKD-stage 3-4.

Intermittent Online Postdilution Hemodiafiltration versus High-Flux Hemodialysis in Non-critical Acute Kidney Injury: A Pilot Randomized Controlled Trial.

The preferential use of convective modes of hemodialysis (HD) for targeting hyper-cytokinemia state in sepsis-related acute kidney injury (AKI) has been questioned for its efficacy. Several studies have used predilution hemodiafiltration (HDF) in critically ill AKI patients with mixed results. In this study, we compared intermittent online postdilution HDF with the standard high-flux (HF) intermittent HD in non-critically ill patients with community-acquired (CA) AKI. In this pilot study, stable patients with CA AKI and systemic inflammatory response syndrome were included and given either postdilution online-HDF (OL-HDF) or standard HF HD outside intensive care units. The primary objectives were to assess the feasibility of conducting the study at a larger scale and to detect the differential impact of convective clearance on the rates of independence from dialysis at discharge or after 30 days. Plasma cytokine clearance was assessed as a secondary objective. Eighty consecutive AKI patients were randomized to receive dialysis in one of the treatment arms after fulfilling the eligibility criteria. The baseline parameters of clinical severity, etiology, and indications of dialysis, plus the baseline plasma cytokine profiles, were comparable. Moreover, 83% in the control arm and 71.1% in the intervention arm became independent from dialysis at discharge or at 30 days (P = 0.189). No survival advantage of postdilution OL-HDF was observed (P >0.05). Similar plasma cytokine clearance levels were noted in both arms. The current study confirms the feasibility; however, it does not support the preferential use of postdilution OL-HDF over HF-HD in non-critical patients.

Chronic Kidney Disease Burden in Low-Resource Settings: Regional Perspectives.

The burden of chronic kidney disease (CKD) has increased exponentially worldwide but more so in low- and middle-income countries. Specific risk factors in these regions expose their populations to an increased risk of CKD, such as genetic risk with APOL1 among populations of West African heritage or farmers with CKD of unknown etiology that spans various countries across several continents to immigrant/indigenous populations in both low- and high-income countries. Low- and middle-income economies also have the double burden of communicable and noncommunicable diseases, both contributing to the high prevalence of CKD. The economies are characterized by low health expenditure, sparse or nonexistent health insurance and welfare programs, and predominant out-of-pocket spending for medical care. This review highlights the challenges in populations with CKD from low-resource settings globally and explores how health systems can help ameliorate the CKD burden.

Membranoproliferative glomerulonephritis: A rare presentation of occult filariasis.

Parasitic infections do not usually present with rapidly progressive renal failure but can provoke glomerular lesions which are mostly proliferative. In filarial infection, glomerular involvement is usually mild and transient, and presentation with renal failure is rare. We report occult filariasis presenting as rapidly progressive renal failure due to immune-complex mediated membranoproliferative glomerulonephritis. Our patient responded to treatment with diethylcarbamazine and a short course of steroid. This case highlights the importance of thorough workup to identify the cause and consideration of filariasis in an endemic area.

Extending the ambit of SGLT2 inhibitors beyond diabetes: a review of clinical and preclinical studies on non-diabetic kidney disease.

INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel antidiabetic agents with overwhelming cardiorenal protection. Recent trials focusing on the nephroprotective role of SGLT2i have underscored its success as a phenomenal agent in halting the progression of kidney disease in patients with and without Type 2 diabetes mellitus. Multitudes of pleiotropic effects on tubules have raised hopes for reasonable nephroprotection beyond the purview of the hyperglycemic milieu. AREA COVERED: This review summarizes various animal and human data as evidence for the utility of SGLT2i in non-diabetic chronic kidney disease (CKD). Web-based medical database entries were searched. On the premise of existing evidence, we have discussed mechanisms likely contributing to nephroprotection by SGLT2i in patients with non-diabetic CKD. EXPERT OPINION: Further elucidation of mechanisms of nephroprotection offered by SGLT2i is required to extend its use as a nephroprotective agent. The use of non-traditional markers of kidney damage in future studies would improve the evaluation of their role in attenuating CKD progression. Emerging animal data support the early use of SGLT2i in states of modest proteinuria for superior outcomes. Future long-term trials in patients should aim to address the time of intervention with SGLT2i during the natural disease course of CKD for best outcomes.

Primary membranous nephropathy in children and adolescents: a single-centre report from South Asia.

BACKGROUND: Unlike adults, primary membranous nephropathy (PMN) comprises only 1-2% of childhood nephrotic syndrome. The clinical behaviour of PMN in children is not explicit and we report upon clinical presentation and outcome. METHODS: This prospective study includes children and adolescents (< 20 years) with biopsy-proven PMN without secondary causes. Anti-PLA2R assessment: before and after completing therapy. OUTCOME: percentage of patients achieving remission. RESULTS: Study cohort included 48 (M:F ratio 1.1:1) patients and median age 17 (IQR 15-18) years, with 35 (72.9%) PLA2R related. Median interval from symptom onset to presentation was 5 months, where median proteinuria, serum albumin and creatinine were 4.9 g/day, 2.1 g/dL and 0.63 mg/dL, respectively. Forty-seven patients received immunosuppressive therapy, with various agents used as first-line therapy: cyclical CYC/GC (53.1%), CNI/GC (21.3%), rituximab (14.9%), prednisolone alone (4.3%), azathioprine (4.3%) and mycophenolate mofetil (2.1%). Median follow-up was 29 (14, 59) months. At 6 months, 11 (24.4%) and 17 (37.7%) had complete remission (CR) or partial remission (PR), while at last follow-up (median 29 months), 20 (45.4%) and 14 (31.8%) had CR and PR respectively. No significant differences in outcome were observed with different agents. A total of 60% patients treated with rituximab as first line/for relapsing disease, and all cases with resistant disease receiving rituximab had CR or PR at last follow-up. PLA2R antibody presence was associated with clinical outcome. CONCLUSIONS: Three-quarters of PMN in children and adolescents is PLA2R related and two-thirds respond to immunosuppressive therapy. Rituximab is a promising agent to manage PMN in children. Anti-PLA2R is associated with clinical outcomes.

Levofloxacin based non-rifampicin anti-tuberculous therapy: An effective alternative in renal transplant recipients in resource limited setting.

INTRODUCTION: Rifampicin is one of the most effective components of anti-tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post-renal transplant recipient, the dose of calcineurin inhibitors needs to be up-regulated and frequently monitored. In resource-limited (low- and lower-middle-income countries) setting this is not always feasible. Therefore, we evaluated a non-rifampicin-based ATT using levofloxacin in kidney transplant recipients. METHODS: We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non-rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. RESULTS: Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1-228) months following transplantation, of them, 64 patients opted for non-rifampicin-based ATT. The mean age was 37.6 years. Only 25% were given anti-thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus-based triple-drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. CONCLUSION: Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage.

Postpartum Renal Cortical Necrosis Is Associated With Atypical Hemolytic Uremic Syndrome in Developing Countries.

INTRODUCTION: Pregnancy-related acute kidney injury is the most common cause of renal cortical necrosis (RCN). Atypical hemolytic uremic syndrome (aHUS) as a cause of RCN in pregnant/postpartum is underevaluated. In the current article, we describe a series of cases of pregnancy-related RCN. METHODS: All cases with acute kidney injury (AKI) in the setting of pregnancy and postpartum state were included. Diagnosis of RCN was made by contrast-enhanced computerized tomography (nonenhancing renal cortex, enhancing medulla, and no excretion of contrast medium) or on a renal biopsy. aHUS was diagnosed in the presence of microangiopathic hemolytic anemia (thrombocytopenia, elevated lactate dehydrogenase with schistocytes on peripheral smear examination, or low haptoglobin). RESULTS: A total of 21 (17.5%) patients presented with RCN during pregnancy, all in the postpartum state. Twenty patients (95.2%) showed microangiopathic hemolytic anemia consistent with HUS and 1 (4.8%) patient had biopsy-proven thrombotic microangiopathy. Low complement 3 or activation of an alternate complement pathway was seen in 9 of 15 patients in which it was done. At the end of 6 months, only 2 (9.5%) patients had partial recovery of renal functions, 5 (23.8%) patients died, and 14 remained (66.7%) on hemodialysis. CONCLUSION: The clinical and laboratory features are highly suggestive of aHUS in more than three-fourths of cases with postpartum RCN. Investigations are needed to look for genetic abnormalities in the complement pathway.