Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study.

Objective: Loss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD). Methodology: The cross-sectional study included individuals who reported having no evidence of chronic kidney disease (CKD). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to assess kidney function. eGFR was calculated using the 2009 CKD-EPI (CKD-Epidemiological) equation. WT1 was analyzed in uE from humans and Wistar rats (before and after the 9th week of diabetes, n = 20). uE-WT1, urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were estimated using ELISA. The Kruskal-Wallis H test, Mann-Whitney U test, and stepwise multivariable linear regression were performed. Results: Urine NGAL and ACR increase with uE-WT1 quartiles (n = 146/quarter). Similarly, uE-WT1, KIM-1, and NGAL were positively associated with ACR. Furthermore, KIM-1, NGAL, and uE-WT1 correlated with ACR. uE-WT1 outperformed KMI-1 and NGAL to explain ACR variability (25% vs. 6% or 9%, respectively). Kidney injury in streptozotocin-induced diabetic rats was associated with a significant rise in uE-WT1. Moreover, the findings were confirmed by the histopathology of kidney tissues from rats. Conclusion: uE-WT1 was strongly associated with kidney function in rats. In individuals without CKD, uE-WT1 outperformed NGAL as a determinant of differences in ACR.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Background: Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. Objective: This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). Materials and Methods: A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. Discussion: PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. Results: A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Conclusion: Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

Liver Stiffness is Reduced to Normal After Successful Renal Transplantation: A Prospective Cohort Study.

Background: Liver stiffness (LS) may be falsely elevated in patients on maintenance hemodialysis (MHD) due to fluid overload. We measured LS change by transient elastography (TE) in MHD patients before and after successful renal transplantation. Method: Adults on ≥2 years of MHD, without additional risk factors for liver fibrosis or fluid overload, and planned for renal transplantation were prospectively recruited. LS was measured on two occasions, i.e., within two weeks before transplantation (pre-Tx LS) and after ≥ 3 months after successful transplantation (post-Tx LS). The participants with pre-Tx LS ≤ 7.0 KPa and >7.0 KPa were classified as "Group I" and "Group II," respectively. Categorical and numerical data are expressed as ratio/proportions and mean (SD), respectively. Results: Paired data from 43 participants (males 42 [97.7%]; age 32 [11] years) were analyzed. The pre-Tx and post-Tx LS of the entire cohort, measured at 307 (198) days of interval, were 8.5 (7.3) KPa and 6.7 (3.1) KPa, respectively. Before transplantation, 21 (49%) participants belonged to Group II and 22 (51%) to Group I. Among the Group II participants, 12 (57%) showed LS normalization after 312 (182) days of transplantation. Of the 22 participants in Group I, three (13.6%) showed LS elevation to >7.0 KPa after 303 (217) days of transplantation. The mean LS changes among the overall cohort, Group II, and Group I were -1.8 KPa, -4.1 KPa, and +0.2 KPa, respectively. Conclusion: LS in people on MHD may be falsely elevated, which is likely to normalize after successful renal transplantation.

Antibody Response to ChAdOx1 nCoV-19 (AZD1222) Vaccine in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) are at a much higher risk of complications and death following COVID-19 and are poor vaccine responders. The data are limited on the immune response to Covishield® in KTRs. We prospectively recruited a cohort of 67 KTRs aged >18 between April 2021 and December 2021. Each participant was given two intramuscular doses of Covishield®, each of 0.5 mL, at an interval of 12 weeks. A blood specimen of 5.0 mL was collected from each participant at two points within a few days before administering the first dose of the vaccine and at any time between 4−12 weeks after administering the second dose. The sera were tested for anti-RBD antibody (ARAb) titre and neutralising antibody (NAb). An ACE2 competition assay was used as a proxy for virus neutralization. According to the prior COVID-19 infection, participants were grouped as (i) group A: prior symptomatic COVID-19 infection, (ii) group B: prior asymptomatic COVID-19 infection as evidenced by detectable ARAb in the prevaccination specimen, (iii) Group C: no prior infection with COVID-19, (iv) group D: Unclassified, i.e., participants had no symptoms suggestive of COVID-19, but their prevaccination specimen was not available for ARAb testing before vaccination. Fifty of sixty-seven participants (74.6%) provided paired specimens (group A 14, group B 27, and group C 9) and 17 participants (25.4%) provided only postvaccination specimens (group D). In the overall cohort (n = 67), 91% and 77.6% of participants developed ARAb and NAb, respectively. Their ARAb titre and NAb proportion were 2927 (520−7124) U/mL and 87.9 (24.4−93.2) %, respectively. Their median ARAb titre increased 65.6 folds, from 38.2 U/mL to 3137 U/mL. Similarly, the proportion of participants with NAb increased from 56% to 86%, and the NAb proportion raised 2.7 folds, from 23% to 91%. A comparison of vaccine response between the study groups showed that all those with or without prior COVID-19 infection showed a significant rise in ARAb titre (p < 0.05) and NAb proportion (p < 0.05) after the two doses of vaccine administration. The median value of folds rise in anti-RBD and NAb between groups A and B were comparable. Hence, ARAb is present in more than 3/4th of KTRs before the ChAdOx1 vaccine in India. The titer of ARAb and the proportion of NAb significantly increased after the two doses of the ChAdOx1 vaccine in KTRs.

Aftermath of fortnightly universal testing for severe acute respiratory corona virus-2 infection in maintenance hemodialysis patients.

INTRODUCTION: Asymptomatic maintenance hemodialysis patients with acute respiratory corona virus-2 (SARS-COV-2) are missed with pre-dialysis screening without testing. The possible ideal strategy of testing each patient before each shift with reverse transcription polymerase chain reaction (RT-PCR) is not feasible. We aimed to study the effectiveness of fortnightly screening with RT-PCR for SARS-CoV-2 in curbing transmission. METHODS: Between July 1, 2020 and September 30, 2020, all 273 patients receiving hemodialysis were subjected to fortnightly testing for SARS-Cov-2 in the unit to detect asymptomatic patients. The cost and effectiveness of universal testing in preventing transmission were analyzed using susceptible-infectious-removed (SIR) modeling assuming R0 of 2.2. RESULTS: Of 273 MHD patients, 55 (20.1%) found infected with SARS-CoV-2 over 3 months. Six (10.9%) were symptomatic, and 49 (89.1%) asymptomatic at the time of testing. Six (10.9%) asymptomatic patients develop symptoms later, and 43 (78.2%) remained asymptomatic. A total of seven (6.1%) HCWs also tested positive for the virus. Fortnightly universal testing is cost-effective, and SIR modeling proved effective in preventing person-to-person transmission. CONCLUSIONS: Repeated universal testing in maintenance hemodialysis patients detected 89% of asymptomatic SARS-CoV-2 patients over 3 months and appeared to be an effective strategy to prevent person-to-person transmission in the dialysis unit.

Acute hepatitis C treatment in advanced renal failure using 8 weeks of pan-genotypic daclatasvir and reduced-dose sofosbuvir.

BACKGROUND: Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30 mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection with hepatitis C virus ( HCV) and eGFR <30 mL/min. METHODS: Clinic records were searched to identify treatment-naïve, noncirrhotic adults with acute hepatitis C (HCV viremia and a ≥10-fold elevation of serum alanine aminotransferase activity) and eGFR <30 mL/min, who had been treated with a sofosbuvir-based regimen. Treatment response was assessed using serum HCV RNA testing at 4 weeks of treatment, end of the 8-week treatment and 12 weeks after stopping treatment. RESULTS: Of the 31 patients with acute hepatitis C, 27 [median age (range): 36 (18-74) years; 20 (74%) male] were started on treatment with 200 mg sofosbuvir and 60 mg daclatasvir daily for 8 weeks, irrespective of HCV genotype. All the 27 completed the planned 8-week treatment. One patient died 10 weeks after completing the treatment of an unrelated cause. All the 27 patients had undetectable HCV RNA after 4 weeks of and at the end of treatment. At 12 weeks after completion of treatment, only one tested HCV RNA positive and 25 were negative, with sustained virological response rate of 25/27 (92.6%) and 25/26 (96.2%) on intention-to-treat and per-protocol basis, respectively. CONCLUSION: Eight-week course of daclatasvir and half-dose sofosbuvir is effective for acute hepatitis C in patients with eGFR <30 mL/min and could be a useful alternative to costly, kidney-safe anti-HCV oral drugs in resource-constrained settings.

Clinical Characteristics, Patient and Technique Survival in Elderly Patients on Peritoneal Dialysis.

The outcomes of the elderly population on peritoneal dialysis (PD) in developing countries are less known. In this study, we intended to study the clinical characteristics and patient and technique survival of elderly patients on PD. In this study, data of 148 elderly patients with end-stage renal disease who initiated PD between January 2001 and December 2015 were collected. Baseline clinical characteristics and events during the study period were recorded. Overall patient and technique survival rates of diabetic and non-diabetic elderly patients on PD were analyzed. Around 128 patients who were initiated PD during the study period were included for final analysis. The mean age of the study group was 70.3 ± 5.1 years, and 94 (80%) were males. Among these, 79 (65.8%) had diabetes. At the end of the study period, only 20 (16.6%) patients were remained on PD. Eighty-four (70%) patients died during PD and 15 (12.5%) patients were transferred to hemodialysis during the study period. The main reasons for death were cardiovascular (56.6%) and sepsis due to peritonitis (18.8%). The mean patient survival time was 38.2 ± 2.6 months. The patient survival rates were 91.2%, 45.3%, and 22.8% at 1, 3, and 5 years, respectively. Predictors of mortality were increased serum phosphorus, peritonitis episodes, urine output <400 mL, and ultrafiltration <1000 mL/day at beginning of PD. The mean technique survival time was 92.0 ± 5.1 months. Technique survival rates at 1, 3, and 5 years were 94.8%, 85.3%, and 71.7%, respectively. None of the factors was found to be predictive of technique survival. We found no significant difference between diabetic and non-diabetic patients in terms of technique and patient survival. Mortality was higher in elderly patients on PD. Factors affecting mortality in elderly patients on PD are low urine output, low ultrafiltration at beginning of PD, high serum phosphorus, and presence of peritonitis episodes. Patient and technique survival rates were comparable between diabetic and non-diabetic elderly patients on PD.

Daclatasvir and reduced-dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min.

AIM: Sofosbuvir is a key agent for HCV treatment. It is not recommended for patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 mL/min. We report real-life experience of treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half-daily dose of sofosbuvir. METHODS: Adults patients who (i) had eGFR<30 mL/min and detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA based regimens were included. All patients were treated with daily doses of daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12 weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or on immunosuppressive drugs. The end-points of the study were: (i) 12 weeks of follow-up after treatment completion, (ii) treatment discontinuation, or (iii) death or loss to follow-up. RESULTS: Thirty-six (88%) among 41 included patients (median [range] age: 48 [19-75] years; 25 [61%] male; genotype 1/3/4 were 17/ 22/2; cirrhosis 5) completed the treatment, two discontinued and three died during treatment. On an intention-to-treat basis, HCV RNA were undetectable at 4 weeks of treatment, treatment completion and after 12 weeks of follow-up in 40/41 (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had a relapse. CONCLUSIONS: Daclatasvir and half-daily dose of sofosbuvir was effective against genotype 1 and 3 HCV infection in patients with eGFR <30 mL/min. This combination could be a pangenotypic treatment option for such patients.