The Association of Lower Levels of Baseline Proteinuria With Earlier Remission in Primary Membranous Nephropathy.

Aim To study the clinical profile and course and to assess the outcome of patients with biopsy-proven primary membranous nephropathy (MN). Methods This study was carried out in a tertiary care hospital between December 2017 and December 2021 on four-year retrospective biopsy-proven patients with membranous nephropathy (MN). Urinary proteins, serum albumin, and serum creatinine were the baseline investigations that were performed. Special tests were done whenever necessary. Patients were treated with a modified Ponticelli (MP) regimen whenever needed. Patients were followed up after treatment administration for a minimum of a year. Results The study was done in 48 biopsy-proven MN patients. Thirty-six patients had primary MN with a mean age of 47+/-11.7 years. The male-female ratio was 2.6:1. Hypertension was present in 39% (14 patients), microscopic hematuria in 28% (10 patients), and acute kidney injury in 22% (8 patients). The mean 24-hour urinary protein was 11.2+/-2.9 g/day. PLA2R was positive in 78% (28 patients) of primary MN patients. Spontaneous remission was noted in 13.8% (5 patients) who were treated conservatively. Spontaneous remission was associated with lower baseline proteinuria (p<0.001), higher baseline serum albumin (p<0.001), and PLA2R negativity (p=0.04). Complete or partial treatment response was noted in 74.2% (23 patients). Treatment remission was associated with lower baseline proteinuria (p=0.018). Secondary membranous nephropathy (secondary MN) was diagnosed in 12 patients. Eleven were class V lupus nephritis, all women, and one male person living with HIV/AIDS (PLHA). Conclusions The majority of our primary MN patients were PLA2R positive on renal biopsy. Statistically significant factors associated with spontaneous remission were lower proteinuria, higher serum albumin at baseline, and PLA2R negativity. Treatment response was associated with lower proteinuria at presentation. The most common cause of secondary MN was lupus nephritis.

Community-acquired acute kidney injury in India: data from ISN-acute kidney injury registry.

Background: Acute kidney injury (AKI), particularly community-acquired AKI (CA-AKI), is a major health concern globally. The International Society of Nephrology's "0 by 25" initiative to reduce preventable deaths from AKI to zero by 2025 is not achievable in low and middle income countries, such as India, possibly due to a lack of data and measures to tackle this urgent public health issue. In India, CA-AKI predisposes younger patients to hospitalization, morbidity, and mortality. This is the first multicenter, prospective, cohort study investigating CA-AKI and its consequences in India. Methods: This study included data from patients with CA-AKI (>12 years of age) housed in the Indian Society of Nephrology-AKI registry, involving 9 participating tertiary care centers in India, for the period between November 2016 and October 2019. The etiological spectrum and renal and patient outcomes of CA-AKI at the index visit and at 1-month and 3-month follow-ups were analyzed. The impact of socioeconomic status (SES) on outcomes was also analyzed. Findings: Data from 3711 patients (mean [±SD] age 44.7 ± 16.5 years; 66.6% male) were analyzed. The most common comorbidities included hypertension (21.1%) and diabetes (19.1%). AKI occurred in medical, surgical, and obstetrical settings in 86.7%, 7.3%, and 6%, respectively. The most common causes of AKI were associated with sepsis (34.7%) and tropical fever (9.8%). Mortality at the index admission was 10.8%. Complete recovery (CR), partial recovery (PR), and dialysis dependency among survivors at the time of discharge were 22.1%, 57.7%, and 9.4%, respectively. Overall, at 3 months of follow-up, mortality rate, CR, PR, and dialysis dependency rates were 11.4%, 72.2%, 7.2%, and 1%, respectively. Multivariate analysis revealed that age >65 years, alcoholism, anuria, hypotension at presentation, thrombocytopenia, vasopressor use, transaminitis, and low SES were associated with mortality at the index admission. Interpretation: Sepsis and tropical fever were the most common causes of CA-AKI. Presentation of CA-AKI to tertiary care units was associated with high mortality, and a significant number of patients progressed to CKD. Individuals with a low SES had increased risk of mortality and require immediate attention and intervention. Funding: This study was funded by the Indian Society of Nephrology.

Donor-Derived Cell-Free DNA and Active Rejection in Renal Allografts.

Background: Renal allograft rejection contributes to significant morbidity and graft loss. In this setting, early detection of rejection is of paramount importance, which currently relies on histopathology. A reliable non-invasive marker to predict rejection would make surveillance and decision-making easier. Donor-derived cell-free DNA (dd-Cf-DNA) has recently been reported as an emerging tool to predict rejection noninvasively. The utility of cell-free DNA in clinical practice has so far not been studied in an Indian setting. As it offers direct clinical application, we have chosen to investigate this biomarker as a tool to predict rejection. Materials and Methods: A pilot study with convenient sample size was designed, as this is the first of its kind study so far reported from India. Patients being evaluated with a graft biopsy for graft dysfunction were included. Patients with stable graft function, defined as creatinine within 10% of their best creatinine and no proteinuria for the preceding 12 months, were also included. Ten milliliters of whole blood from each of the recipients was collected in DNA isolation tubes. Two milliliters of donor blood was also obtained in ethylenediaminetetraacetic acid (EDTA) tubes. All recipients also provided a buccal swab. Total cell-free DNA was extracted from 2 ml of recipient plasma using circulating DNA isolation kit. Upon identification of the donor-specific DNA marker for each of the patients from the paired donor sample, presence of the cell-free DNA fraction in the recipient's plasma was detected and quantified. Renal biopsy reports and clinical details were also recorded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were analyzed. Receiver operating characteristic (ROC) curve analysis was also performed. Results: A total of 31 patients were recruited. Twenty patients underwent graft biopsies for graft dysfunction, of which 12 patients had features of active rejection and eight had nonrejection causes of graft dysfunction. Eleven patients with stable graft were included in the study. In our study, dd-Cf-DNA performed best in predicting antibody-mediated rejection (ABMR) and higher grades of T-cell-mediated rejection (TCMR) (1B). It did not detect TCMR 1A accurately. It serves as a good marker to rule out rejection. It gave a NPV of 100% for TCMR 1B or ABMR, 100% for ABMR alone, and 81% for any rejection. dd-Cf-DNA percentages outperform absolute concentrations in their discriminatory ability. Conclusion: We have demonstrated the diagnostic accuracy of dd-Cf-DNA in predicting active rejection of the renal allograft. It performs well in ABMR and higher grades of TCMR. This is the first of its kind study reported from India, to the best of our knowledge. This tool serves as a good rule out test for ABMR and higher grades of TCMR. It performs poorly in TCMR 1A.

Frailty in Patients With Chronic Kidney Disease Stage Five.

Aim To study the prevalence of frailty in patients with chronic kidney disease stage 5 (CKD5) and to assess coexisting factors associated with frailty in chronic kidney disease. Patients and methods We studied the prevalence of frailty in CKD5 patients from November 2021 to November 2022. CKD5 patients over 18 years of age were included. Patients on maintenance hemodialysis and CKD5 patients on pre-dialysis care were included. Patients with active infection and significant morbidity were excluded. We performed a history and clinical examination and recorded laboratory data. We performed frailty assessments using modified Fried's criteria. Frailty was defined based on previously validated Fried's criteria, which included 1. Slowness, 2. Weakness, 3. Unintentional weight loss, 4. Exhaustion, 5. Low physical activity. A patient is considered frail if three or more components are present. We evaluated the prevalence of frailty in pre-dialysis and dialysis care participants and the association of frailty with coexisting factors. Results Of the 139 patients, 84 were on thrice-weekly hemodialysis, and 55 were on pre-dialysis care. We found the prevalence of frailty to be 41%. The prevalence of frailty was similar in patients on pre-dialysis care and hemodialysis. The prevalence of frailty in hemodialysis patients and those in pre-dialysis care was 43% and 40%, respectively. The prevalence of frailty among the elderly (over 55) was 82%. The prevalence of frailty among diabetes patients was 75%. Factors with a statistically significant association with frailty included old age (p < 0.005), native kidney disease (p < 0.005), edema (p < 0.001), intradialytic hypotension (p = 0.002), and various comorbidities like diabetes (p < 0.001), heart failure (p < 0.001), coronary artery disease (p = 0.001), and cerebrovascular accidents (p = 0.016). We observed no significant association with the duration of chronic kidney disease (CKD) (p = 0.458), duration of dialysis (p = 0.838), or body mass index (BMI) (p = 0.267). The most commonly reported frailty components were exhaustion (61.9%), low physical activity (61.2%), and weak handgrip (55.4%). Conclusion Frailty is a marker of increased vulnerability to adverse outcomes. A significant proportion, 41% of CKD5 patients, are frail. Dialysis does not affect the prevalence of frailty in CKD5 patients. Old age, native kidney disease, edema, intradialytic hypotension, and comorbidities like diabetes, heart failure, coronary artery disease, and cerebrovascular accident are significantly associated with frailty in CKD5 patients. CKD patients with those conditions should receive special care to reduce the development of frailty.

Uremic Sarcopenia.

"Uremic sarcopenia" refers to a progressive decrease in muscle mass, strength, and function despite normal skeletal muscle physiology in patients with chronic kidney disease (CKD). Sarcopenia involves multiple risk factors, comprising immunological changes, hormonal, metabolic acidosis, reduced protein intake, and physical inactivity. All these risk factors, along with complex pathophysiological mechanisms including ubiquitin, insulin/IGF-1, myostatin, and indoxyl sulfate, activate downstream pathways that ultimately increase muscle degradation while reducing muscle regeneration. Uremic sarcopenia not only affects the quality of life but also increases the risk of morbidity and mortality in patients with CKD. Of all the treatment modalities, aerobic and resistance exercise have shown prevention and reduced rate of muscle degeneration. A variety of pharmacological agents have been tried to target different steps in the known pathogenetic pathways, including the use of androgens and anabolic steroids, correction of vitamin D deficiency, use of growth hormone supplementation, and suppression of the ubiquitin pathway. Though some of these techniques have had beneficial results in animal experiments, human trials are still sparse. This review article relates to recent publications that describe the abnormalities in skeletal muscle that primarily leads to muscle wasting and its consequences in patients with CKD.

Clinical Profile, Histopathology, and Outcomes in Infection-Related Glomerulonephritis - Single-Center Experience.

Background: Infection-related glomerulonephritis (IRGN) is an important source of renal morbidity with adverse outcomes in adults. Data from large centers in India is lacking on this common, yet poorly understood entity. Materials and Methods: We performed a prospective observational study of all patients diagnosed with IRGN at our center over a 3-year period between 2017 and 2019. "Typical IRGN" patients were diagnosed based on clinical and laboratory assessment; others underwent renal biopsy. Renal and patient survival outcomes were assessed in addition to factors that help predict outcomes. Results: One hundred and twenty-five patients with a diagnosis of IRGN were included in the study, including 86 patients who underwent renal biopsy. This represented 24% of all biopsies during this time period, and IRGN was the most common nondiabetic kidney disease identified in diabetic biopsies at our center. Female preponderance and a seasonal variation were striking. Atypical sources of infection like otomycosis, tooth abscess, and dengue virus infection were noted. Male gender and diabetes were important risk factors for severe disease. Rapidly progressive glomerulonephritis (RPGN), atypical serum complement profiles, and comorbid illnesses were common in adults. Though children had more benign disease and outcomes, life-threatening complications were also noted. C3 dominance was the most striking immunofluorescence (IF) finding and was associated with poorer outcomes. Crescentic IRGN was rare, and four cases of IgA-dominant IRGN were noted. Also, 24% of the cohort required renal replacement therapy. RPGN presentation of IRGN portended worst prognosis with end-stage renal disease (ESRD) in 31% and death in 22% of patients. Conclusion: IRGN is a common clinical entity in adults with the potential for adverse renal and survival outcomes. We have identified clinical and biopsy characteristics that are associated with ESRD and death.

Adenovirus-Associated Thrombotic Microangiopathy and Necrotizing Interstitial Nephritis in a Renal Transplant Recipient: A Case Report and Review.

Adenoviral infections, though rare, may be a source of significant morbidity and mortality in the early post renal transplant period. We present a case of fever and graft dysfunction in a deceased donor renal transplant recipient whose initial post-operative period was complicated by vascular thrombosis and ureteric necrosis. He had received induction immunosuppression with Rabbit-Anti Thymocyte Globulin. Graft biopsy was suggestive of Thrombotic Microangiopathy (TMA) accompanied by intense interstitial inflammation, hemorrhage, necrosis, WBC casts and tubular injury. Viral cytopathic changes were discernible on light microscopy, leading to suspicion of adenoviral infection. This was confirmed with immunohistochemical demonstration of adenoviral antigens in the graft biopsy. He was treated with a step down of immunosuppression and intravenous Immunoglobulin. However, the patient's general condition deteriorated rapidly, and he succumbed to his illness. We highlight this association of TMA and necrotizing tubulo-interstitial nephritis with adenoviral infection of the renal allograft.

Association of IgA Nephropathy with Squamous Cell Carcinoma of the Tongue: - Case Report and Review of Literature.

A 32-year-old habitual tobacco chewer was diagnosed with squamous cell carcinoma of the tongue. He was initiated on chemo-radiation therapy. After completing 23 cycles of radiation and four cycles of cisplatin-based chemotherapy, he presented with acute nephritic syndrome. Renal biopsy showed IgA nephropathy and acute tubular injury. With supportive care, renal function stabilised with a reduction in proteinuria. We wish to highlight the poorly understood association between mucosal malignancies and IgA nephropathy. It is also interesting to note the peculiar temporal profile of glomerular involvement in our patient, where the onset of the glomerulonephritis was after the initiation of chemo-radiotherapy. This is unlike what has been described earlier.

Outcomes of symptomatic coronavirus disease 19 in maintenance hemodialysis patient in India.

BACKGROUND: Maintenance hemodialysis (MHD) patients face disadvantages with higher risk of acquiring SARS-CoV-2 infection, atypical manifestations, and associated multiple comorbidities. We describe patients' outcomes with symptomatic COVID-19 on MHD in a large cohort of patients from India. METHODS: Data were collected prospectively from hemodialysis units in 11 public and private hospitals between March 15, 2020, and July 31, 2020. The survival determinants were analyzed using stepwise backward elimination cox-regression analysis. RESULTS: Of the 263 total patients (mean age 51.76 ± 13.63 years and males 173) on MHD with symptomatic COVID-19, 35 (13.3%) died. Those who died were older (p = 0.01), had higher frequency of diabetic kidney disease (p = 0.001), comorbidities (p = 0.04), and severe COVID-19 (p = 0.001). Mortality was higher among patients on twice-weekly MHD than thrice-weekly (p = 0.001) and dialysis through central venous catheter (CVC) as compared to arteriovenous fistula (p = 0.001). On multivariate analysis, CVC use (HR 2.53, 95% CI 1.26-5.07, p = 0.009), disease severity (HR = 3.54, 95% CI 1.52-8.26, p = 0.003), and noninvasive ventilatory support (HR 0.59, 95% CI 0.25-0.99, p = 0.049) had significant effect on mortality. CONCLUSION: The adjusted mortality risk of COVID-19 in MHD patients is high in patients associated with severe COVID-19 and patients having CVC as vascular access.

Recurrent Seizures in an Adolescent Female-A Daunting Puzzle.

Acute porphyrias are metabolic disorders resulting from deficiency of a specific enzyme involved in heme biosynthetic pathway. These deficiencies also affect normal renal physiology, as kidneys are also involved in heme synthesis. Sometimes, this could even lead to end stage renal disease. Acute Intermittent Porphyria, an autosomal dominant disorder arising from half-normal activity of hydroxymethylbilane synthase, is characterized by occurrence of vague neurovisceral attacks (abdominal pain, nausea, vomiting, constipation and neuropsychiatric symptoms), with urinary excretion of porphyrin precursors, such as 5-Amino-levulinic acid (ALA) and Porphobilinogen (PBG). Acute attacks are triggered by dehydration, diarrhea, steroids, low calorie diets. Treatment includes avoidance of precipitating factors, adequate hydration, high carbohydrate diet and heme replacement. Here, we present an adolescent female who had presented with recurrent abdominal pain, dyselectrolyemia with associated seizures, was diagnosed with Acute Intermittent Porphyria and recovered well with symptomatic management.

An Emergent Cause of Renal Allograft Dysfunction.

Infection-related glomerulonephritis (IRGN) results from an immune-mediated process in the occurrence of non-renal infection. Despite increased incidence of infections post-transplant, which is attributed to the immunosuppression, IRGN serves to be a rare cause of de novo GN. Here, we present a 43-year old male, a deceased donor renal transplant recipient, who presented with acute decline in allograft function that developed in association with IRGN five years after transplant. He continued to have renal allograft dysfunction despite treatment with antibiotics. We infer that IRGN must be thought of as a possible entity, although rare, in the diagnosis of de novo GN post-transplant. Furthermore, the absence of definitive treatment protocol makes this emerging cause of renal allograft dysfunction be associated with the poor prognosis.

The Adverse Effect of COVID Pandemic on the Care of Patients With Kidney Diseases in India.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. METHODS: We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. RESULTS: The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. CONCLUSION: Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

A multicenter study of malnutrition status in chronic kidney disease stages I-V-D from different socioeconomic groups.

There is a paucity of data on malnutrition in different socioeconomic status in chronic kidney disease (CKD) patients. Hence, this cross-sectional study was undertaken in CKD-ND and CKD-D. The aim of the study was to assess the prevalence of malnutrition in the various stages of CKD among the various socioeconomic groups, namely the low-income groups and the upper-middle-income groups. This is a cross-sectional study conducted among 394 patients. The patient data were obtained from three institutions: Institution 1, Institution 2, and Institution 3. Patients were predominantly from the South Indian population and were between the age groups of 18 and 80 years. Measurements: malnutrition was assessed using anthropometry, body composition monitor, biochemical parameters, and dietary recall. Subjective Global Assessment Scale for nondialyzed patients and Malnutrition-Inflammation Score for dialyzed patients were also collected . As per the CKD stages, we found the percentage of malnutrition to be 7% in Stage III, 14% in Stage IV, 18% in Stage V, and 68% in Stage V-D in the upper-middle-income group, whereas it was 10% in Stage III, 26% in Stage IV, 40% in Stage V, and 93% in Stage V-D in the low-income group. The severity of malnutrition was stratified according to the stages of CKD, and it was found to be higher in progressive stages of CKD among the low-income groups as compared to the high-income groups.

Challenges in Management of Disseminated Melioidosis with Endocarditis in a Patient with Chronic Kidney Disease.

Melioidosis is a tropical infection that is increasingly being reported from South India. It is frequently observed in patients with diabetes mellitus, chronic ethanol consumption and chronic kidney disease (CKD). It presents commonly with pneumonia, deep seated abscesses or osteoarticular infections. Cardiac complications are very rare with endocarditis being reported in very few patients. We report the first case of endocarditis in melioidosis in India. Although infections are common in patients with CKD, melioidosis at the time of diagnosis of CKD has never been reported in the past. Our patient had multiple liver abscesses and endocarditis, and responded well to a 6 week course of ceftazidime and doxycycline, with the latter being continued for 20 weeks.

Lupus nephritis in a patient with retroviral infection.

A 38-year-old woman, diagnosed as Person Living with Human Immunodeficiency Virus (HIV) on Highly Active Antiretroviral Therapy (HAART) for three years, presented with features of fever, rashes, joint pain, dyspnea and pedal edema. On evaluation, a diagnosis of Systemic Lupus Erythematosus with Lupus Nephritis (LN) triggered by HIV infection was made based on clinical and serological evidence. She was continued on HAART, and immuno-suppressive therapy was co-administered resulting in the resolution of her symptoms. Lupus-like histopathological findings have been reported in patients with HIV-related kidney diseases. This case report is to highlight the co-existence of LN in a patient with HIV infection.