Augmented mannose-binding lectin levels in primary membranous nephropathy: A pilot study.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.

Single-center Haemodialysis Experience in India During COVID-19.

Introduction: Since COVID-19 has been announced as a pandemic, outcome of dialysis patients in terms of morbidity and mortality from India is lacking. We studied the clinical, epidemiological features of COVID-19 along with outcome in terms of mortality in our dialysis cohort. Methods: Data of End-Stage Kidney Disease (ESKD) patients who were admitted in COVID-19 designated hospital block as positive and suspected patients from 1st April 2020 to 31st July 2020 was retrieved. Data about epidemiological characteristics, clinical features, mortality outcomes of COVID-19 positive and negative patients were analyzed. Results: A total of 97 ESKD patients were admitted during the study period, of which 44 (45.4%) and 53 (54.6%) patients were found to be COVID-19 positive and negative respectively. The mean age of COVID positive patients was 46 years with 54.5% being female. Only three patients (6.8%) remained asymptomatic throughout the course of illness. Amongst COVID-19 positive, 20 (45.45%) were severely ill while 18 (40.9%) were having mild illnesses. Breathlessness (65.9%) and fever (61.4%) were common symptoms. The death occurred in 17 (38.6%) and 25 (47.1%) COVID-19 positive and negative ESKD patients respectively. 14 (82.3%) patients who expired amongst COVID-19 positive were having severe illness and significantly more were associated with negligible residual renal function. Conclusions: Breathlessness and fever were common symptoms amongst COVID-19 ESKD patients. Very few patients remained asymptomatic in our cohort and significantly more mortality is observed in severely ill patients and those with negligible residual renal function.

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.

Continuing arteriovenous fistula creation by nephrologist and its outcome during COVID pandemic-Analysis of 376 cases.

There has been a significant reduction of elective surgeries including creation of arteriovenous fistulas (AVF) during the ongoing pandemic by the surgeons. Here, we report the retrospective observational data of AVF creation by nephrologists in a single center, during a period of 8 months. A total of 376 fistulae were created in 310 patients. Patients were followed up at 2, 6, and 12 weeks. Twenty-eight patients required fistula creation twice, 16 patients thrice, and two patients underwent fistula creation four times. Of the total, 259 (68.8%) fistulae were radio-cephalic while 99 (26.3%) and 18 (4.79%) were brachio-cephalic and brachio-basilic, respectively. A total of 207 (67%) patients were already on hemodialysis whereas 103 (33%) were planned for elective initiation after fistula maturation. Of the 211 (69%) patients who completed 3 months of follow-up, 31 (15%) expired and 7 (3.3%) were lost to follow-up. Primary failure was observed in 70 (33.2%) fistulae. Fifteen (7.1%) patients were noted to be COVID positive during the follow-up. A total of 279 (90%) patients were alive at last follow-up. Amongst 20 dialysis staffs with 10 nephrologists, only two have developed COVID. Both were having mild illness and recovered completely. This study demonstrates that AVF creation can be performed safely with careful screening and by using adequate personal protective equipment.

Longitudinal Study to Find the Association of Serum Phosphorus Level with FGF23 in Three Different Hyperphosphatemia Management Groups of Stage 3 and 4 Chronic Kidney Disease (CKD) Patients.

Background: There is paucity of clinical evidence on target serum phosphorus levels in early chronic kidney disease (CKD). Present longitudinal study was done to find target phosphorus level and its association with fibroblast growth factor (FGF23) in three different hyperphosphatemia management groups. Methods: This 1-year, prospective, randomized controlled, open-labelled study was conducted among three equally allocated treatment groups that consisted of 120 screened early CKD patients totally. Group 1 patients were given dietary phosphorus modification (n = 40), group 2 patients were administered calcium-based phosphate binders (n = 40), and group 3 patients were given non-calcium-based phosphate binders (n = 40). Three-monthly dietary assessment, MDRD estimated glomerular filtration rate (eGFR), phosphorus, calcium, iPTH, alkaline phosphatase, and six-monthly FGF23, 2D echocardiography, and X-ray of chest and abdomen were performed. Association of three categories of phosphorus level up to 3.9, 4-5, and >5mg/dl, rate of progression of all parameters, and correlation with FGF23 were studied among all three groups. Results: At baseline, all clinical and biochemical parameters were equally distributed with a controlled nutritional phosphate among all groups. There was no significant difference of FGF23 levels from all the three categories of phosphorus level among all groups. Serum phosphorus at the level of 5 mg/dl was associated with iPTH and eGFR at 1 year. Over 1 year, there was a significant decline in serum phosphorus levels in group 1 (P 0.02), group 2 (P 0.00), and group 3 (P 0.05). FGF23 declined significantly only in group 3 (P 0.00). There was no correlation of FGF23 with serum phosphorus levels (P 0.13). However, FGF23 correlated positively with iPTH (P 0.03, r = 0.19). Conclusion: Serum phosphorus levels upto 5mg/dl had no effect on FGF23 at early CKD stages. Although different treatment groups showed significant phosphorus reduction, non-calcium phosphate binder had a major impact on FGF23 reduction.

Reversal of endothelial dysfunction post-immunosuppressive therapy in adult-onset podocytopathy and primary membranous nephropathy.

BACKGROUND AND AIMS: The effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. METHODS: Newly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4+CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. RESULTS: Fifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC (p = 0.002) while PWV (p = 0.007), E-selectin (p < 0.001) and CD4+CD28null T cells (p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% (p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s (p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml (p = 0.002) while the CD4+CD28null T cell population reduced from 5.20 to 3.70% (p = 0.032) of total CD4+ cells. In the PMN cohort, despite significant reduction, E-selectin and CD4+CD28null T cells at follow-up remained higher than in healthy controls. CONCLUSION: Immunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN.

Successful re-transplantation in patient with recurrent parvovirus B19 pure red cell aplasia.

Impaired cell-mediated, as well as antibody-mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re-transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re-transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re-consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.

Membranous nephropathy with light chain restricted deposits.

The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M-type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow-up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow-up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non-malignant associated MN with monoclonal deposits on IF.