Comprehensive evaluation of bone health among kidney transplant recipients - A prospective, single center, observational cohort study from India.

BACKGROUND: There is a paucity of studies describing trabecular bone score (TBS) and bone mineral density (BMD) in kidney transplant (KT) recipients from developing countries. STUDY SETTING: This prospective observational study, from a tertiary teaching hospital in India assessed clinical, biochemical parameters including bone turnover markers and dual-energy X-ray absorptiometry (DXA) for BMD/TBS, hip structural analysis (HSA) and vertebral fracture assessment (VFA) at pre-KT, 3 months and 12 months post-KT. RESULTS: A total of 53 KT recipients (90.6% living related) were recruited from August 2019 to March 2020 and followed till 1-year post-KT. The mean age was 33.9±10.4 years, 71.7% were males, and 11.5% had a history of pre-KT steroid use. Baseline fractures pre-KT as assessed by VFA were seen in 4 patients (7.5%). Mean BMD at spine and femoral neck and HSA variables at narrow neck and femoral shaft continued to decline till 3 months, but stabilised and reached pre-KT values 12 months post-KT. However, TBS and bone turn over markers continued to decline till 12 months post-KT (p value <0.001). New onset vertebral fractures were seen in 2(3.7%) and 1 patient (2.3%) at 3- and 12-months post-KT respectively. Pre-KT BMD significantly influenced bone health at 12 months post-KT, with patients in each quartile maintaining a similar trajectory over the follow up period (p < 0.001). CONCLUSION: Despite significant improvement in kidney function following transplant, TBS and BMD of the spine significantly decreased mainly in the early post-KT period suggesting the effect of immunosuppressants on the bone. Strategies to improve bone health in KT patients are warranted.

Bacterial infection-related glomerulonephritis in patients with diabetes.

AIM: Diabetic patients are prone to infections, thus making them a unique cohort at risk of developing bacterial infection-related glomerulonephritis (IRGN). METHODS: In total, 1693 adult diabetic patients underwent kidney biopsy between 2005 and 2021 at our tertiary care hospital in South India. Of these, 121 consecutive cases which met criteria of bacterial IRGN were included in this study. RESULTS: The mean age of the cohort was 53.1 ± 10.1 years and 83/121 (68.5%) were males. Majority (98.3%) had type 2 diabetes for a median duration of 6 (IQR, 2-12) years. The most common sites of infection were skin (47/121, 38.8%) and urinary tract (15/121, 12.4%). Fifty percent (58/121) of patients had underlying advanced diabetic kidney disease (DKD). Isolated C3 deposits (without immunoglobulin) occurred in 66/121 (54.5%) patients predominantly in advanced DKD patients. IgA-dominant glomerulonephritis occurred in only 9/121 (7.4%) patients. Short-course oral steroid was given to 86/121 (71.1%) patients. Steroid related dysglycemia and immunosuppression related infections occurred in 9/61 (14.8%) and 16/61 (26.2%) patients respectively. Of the 90 patients with follow up details >3 months, 46 (51.1%) progressed to kidney failure over a median period of 0.5 (IQR, 0-7.2) months. Patients diagnosed in the latter half of our study period (2013-2021) were older, less commonly presented with fever, had more pronounced hypocomplementemia and severe renal histology predominantly with a 'starry sky' immunofluorescence pattern. CONCLUSION: Superimposed bacterial IRGN on underlying DKD is associated with poor renal outcomes. Use of short course steroid was associated with significant toxicity.

Whole and cortical kidney volume predict 5-year post-nephrectomy eGFR in Indian living kidney donors.

AIM: To study the additional utility of pre-nephrectomy whole and cortical kidney volumes (WKV, CKV) in predicting long-term post-nephrectomy kidney function in Indian living kidney donors (LKDs). METHODS: This retrospective cohort study included all LKDs who underwent nephrectomy between 1 January 2006 and 31 December 2015 at our centre, had pre-nephrectomy height, weight and computed tomography (CT) angiography with arterial and nephrographic phase documented, and 5-year post-nephrectomy creatinine values measured. Correlation between body surface area (BSA) adjusted pre-nephrectomy total CKV, WKV and pre-nephrectomy CKD EPI eGFR; BSA-adjusted remnant pre-nephrectomy CKV (rCKV), WKV (rWKV) and 5-year post-nephrectomy CKD EPI creatinine eGFR (5yeGFRCr ); predictors of 5yeGFRCr < 70% of pre-nephrectomy CKD EPI creatinine eGFR (pre-eGFRCr ), and an equation to predict 5yeGFRCr from pre-nephrectomy variables were calculated. RESULTS: A total of 196 LKDs (74% female, mean age 41.7 ± 11.0 years) were included in the study. Total WKV showed higher correlation with pre-nephrectomy eGFR than CKV, the highest with CKD EPI cystatin eGFR. Remnant WKV showed higher correlation than rCKV with post-nephrectomy eGFRCr and this increased over time. Older age, lower rWKV or rCKV, higher BSA, and higher pre-eGFRCr identified LKDs with 5yeGFRCr < 70% of pre-eGFRCr , with rCKV identifying a higher proportion (4.5%) of such LKDs. A model including rWKV or rCKV predicted 5yeGFRCr better than one including age, gender, BSA and pre-eGFRCr alone. CONCLUSION: Inclusion of pre-nephrectomy remnant CKV and WKV into models for 5yeGFRCr and sub-optimal post-nephrectomy adaptation in Indian LKDs improves their accuracy. CKD EPI cystatin eGFR correlates better with functional renal mass.

Laboratory and clinical comparison of the efficacy of prestorage leukoreduction of red cells at cold versus room temperature.

BACKGROUND: The temperature at which filtration takes place has been reported to influence the efficacy of leukoreduction. We aimed to compare the residual leukocyte count (RLC) in red cell units (RCUs) filtered at cold (CT) versus room temperature (RT) and to assess whether this correlates clinically with a difference in the incidence of acute transfusion reactions (ATRs). METHODS AND MATERIALS: In the first part of the study, whole blood units collected were randomly allocated for subsequent filtration at CT and RT, respectively. RLC postfiltration was assessed using flow cytometry. The second part of the study was a nonrandomized clinical trial in which incidence of ATR was compared between RCUs filtered at RT and CT for 6 months each. RESULTS: Thirty-five RCUs each underwent leukofiltration at CT and RT, respectively. The median RLCs in the filtered units at CT and RT were 0.02 × 106 and 0.1 × 106 leukocytes/unit, respectively (p = .0001), with no difference in red blood cell (RBC) recovery (p = .41). During the second part, 3455 RCUs filtered at RT and 3539 RCUs filtered at CT were transfused to patients. The rate of febrile non-hemolytic transfusion reaction (FNHTR) among transfused patients was less with units filtered at CT (1 per 2000 transfusions) in comparison to RT (1 per 588 transfusions). The difference was, however, not significant (p = .14). CONCLUSION: If change in temperature alone can cause significant reduction in leukocytes, then it is a simple way to curtail the rate of this common yet unpleasant reaction and reduce the reaction rate at minimal cost.

Post-transplant complications, patient, and graft survival in pediatric and adolescent kidney transplant recipients at a tropical tertiary care center across two immunosuppression eras.

BACKGROUND: We report pediatric PAKT patient and graft outcomes at a large tropical tertiary center spanning two transplant eras. METHODS: In this retrospective cohort study, all children ≤18 years who underwent kidney transplantation at our center between 1991 and 2016 were included. Data pertaining to their baseline characteristics, post-transplant events, and outcome were retrieved from transplant records and compared between transplant eras (1991-2005 and 2006-2016). RESULTS: A total of 139 children (mean age 15.2 ± 2.9 years) underwent PAKT during this period. The incidence of UTIs, CMV disease, BKVN, invasive fungal infections, new-onset diabetes after transplant, leucopenia, and recurrent NKD was higher in the 2006-2016 era (P < .001 for all), while 1-year cumulative BPAR was comparable (P = .100). Five-year graft and patient survival in the two eras were 89.9% and 94.2% (P = .365) and 92.1% and 95.3% (P = .739), respectively. Incidence of CMV disease, BKVN, graft loss, and death was lower in the calcineurin withdrawal group. Non-adherence accounted for 36% of graft loss; infections caused 43.7% of deaths. On multivariate Cox proportional hazards analysis, independent predictors for graft loss were UTIs and blood transfusion naïve status and for death were serious infections and glomerular NKD. CONCLUSIONS: PAKT in India has excellent long-term graft outcomes, though patient outcomes remain suboptimal owing to a high burden of infections. Current immunosuppression protocols need to be re-examined to balance infection risk, graft, and patient survival.

Safety and utility of kidney biopsy in patients with estimated glomerular filtration rate < 30 ml/min/1.73 m2.

AIM: Kidney biopsy (KBx) is the gold standard for evaluation of kidney disease, but is associated with a higher risk of complications in patients with reduced glomerular filtration rate (GFR). We studied the safety and utility of KBx in patients with eGFR <30 ml/min/1.73 m2 . METHODS: Consecutive adult patients with eGFR <30 ml/min/1.73 m2 , who were planned for a KBx and consented to participate were prospectively enrolled. Patients with solitary/transplant kidney or acute kidney injury were excluded. Haemoglobin was checked on the day of KBx and repeated 18-24 h later along with a screening ultrasound. Post-KBx complications were noted and their risk-factors analysed. The utility of the KBx was graded as effecting significant, some, or no change to subsequent management. RESULTS: Of the 126 patients included, 75% were male, 27.7% were diabetic, and the median eGFR was 13.5 ml/min/1.73m2 . Major complications occurred in 5.6%. Peri-renal haematomas were detected in 37.3%, and haematomas ≥2 cm were significantly more frequent in those with eGFR <15 ml/min/1.73 m2 (29.2% vs. 13%, p = .032). Dialysis was a risk factor, while pre KBx blood transfusion, diabetes and higher serum albumin were protective against any complication. KBx was more likely to make a significant difference in management in those with eGFR 15-29 ml/min/1.73m2 (44.1% vs. 11.1%, p < .001). Increasing age, lower serum creatinine and albumin were independently associated with KBx utility. CONCLUSION: KBx is relatively safe in severe kidney disease but its risk to benefit balance needs to be carefully considered when eGFR is <15 ml/min/1.73m2 .

Peritoneal dialysis: Status report in South and South East Asia.

BACKGROUND: Peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) is largely underutilized globally. We analyzed PD utilization, impact of economic status, projected growth and impact of state policy(s) on PD growth in South Asia and Southeast Asia (SA&SEA) region. METHODS: The National Nephrology Societies of the region responded to a questionnaire on KRT practices. The responses were based on the latest registry data, acceptable community-based studies and societal perceptions. The representative countries were divided into high income and higher-middle income (HI & HMI) and low income and lower-middle income (LI & LMI) groups. RESULTS: Data provided by 15 countries showed almost similar percentage of GDP as health expenditure (4%-7%). But there was a significant difference in per capita income (HI & HMI -US$ 28 129 vs. LI & LMI - US$ 1710.2) between the groups. Even after having no significant difference in monthly cost of haemodialysis (HD) and PD in LI & LMI countries, they have poorer PD utilization as compared to HI & HMI countries (3.4% vs. 10.1%); the reason being lack of formal training/incentives and time constraints for the nephrologist while lack of reimbursement and poor general awareness of modalities has been a snag for the patients. The region expects ≥10% PD growth in the near future. Hong Kong and Thailand with 'PD first' policy have the highest PD utilization. CONCLUSION: Important deterrents to PD underutilization were lack of PD centric policies, lackadaisical patient/physician's attitude, lack of structured patient awareness programs, formal training programs and affordability.

Association of prior sensitizing events with anti-human leukocyte antigen antibodies: An analysis of renal transplant recipients in a tertiary care centre in South India.

Traditionally, sensitizing events such as previous pregnancies, previous transfusions and prior transplants result in the production of anti-Human Leukocyte Antigen (HLA) antibodies. However, it has been observed that, anti-HLA antibodies have been detected in many patients with no prior history of sensitizing events. This retrospective study analysed the most recent 100 consecutive Single Antigen Bead (SAB) assay results performed on 100 patients. The SAB assay is used routinely to detect anti-HLA antibodies in transplant recipients. Results of the SAB assay were analyzed and subsequently studied to see if a correlation existed between sensitizing events, the type of events and presence of antibody. Analysis showed that 77% (77/100) had anti-HLA antibodies. 61 out of 100 patients had prior sensitizing events while the remaining 39 had none. Both these groups showed an almost equal percent of patients with anti-HLA antibodies 77% (47/61) and 76.9% (30/39) respectively. A single sensitizing event was seen in 54.1% (33/61) patients including previous transfusions in 29.5% (18/61), pregnancies in 11.4% (7/61) and prior transplant in 13.1% (8/61). Our study suggests that irrespective of whether patients have prior sensitizing events or not, patients run the risks of alloimmunization, and therefore appropriate screening tests should be included in the pre-transplant compatibility algorithm.

Developing nephrology services in low income countries: a case of Tanzania.

BACKGROUND: The burden of kidney diseases is reported to be higher in lower- and middle-income countries as compared to developed countries, and countries in sub-Saharan Africa are reported to be most affected. Health systems in most sub-Sahara African countries have limited capacity in the form of trained and skilled health care providers, diagnostic support, equipment and policies to provide nephrology services. Several initiatives have been implemented to support establishment of these services. METHODS: This is a situation analysis to examine the nephrology services in Tanzania. It was conducted by interviewing key personnel in institutions providing nephrology services aiming at describing available services and international collaborators supporting nephrology services. RESULTS: Tanzania is a low-income country in Sub-Saharan Africa with a population of more than 55 million that has seen remarkable improvement in the provision of nephrology services and these include increase in the number of nephrologists to 14 in 2018 from one in 2006, increase in number of dialysis units from one unit (0.03 unit per million) before 2007 to 28 units (0.5 units per million) in 2018 and improved diagnostic services with introduction of nephropathology services. Government of Tanzania has been providing kidney transplantation services by funding referral of donor and recipients abroad and has now introduced local transplantation services in two hospitals. There have been strong international collaborators who have supported nephrology services and establishment of nephrology training in Tanzania. CONCLUSION: Tanzania has seen remarkable achievement in provision of nephrology services and provides an interesting model to be used in supporting nephrology services in low income countries.

Renal transplantation into optimized abnormal lower urinary tract - Impact on graft outcomes, patient survival, and complications.

INTRODUCTION: Literature regarding the outcomes of renal transplant in patients with abnormal lower urinary tracts (LUTs) is conflicting. The study aimed to determine the graft outcomes and complications of renal transplantation in an optimized abnormal LUT as compared to those with a normal LUT. MATERIALS AND METHODS: In this single-center retrospective-matched cohort study, we identified 31 patients with an optimized abnormal LUT in our transplant database between 2006 and 2016 (Group A) and selected an equal number of matched controls (Group B). The primary outcome was graft survival, and secondary outcomes were overall survival and complications. RESULTS: The median age was 24 years (range: 12-45), and the median duration of follow-up was 36 months in both groups. On Kaplan-Meier analysis, the estimated mean graft survival was 106 months (confidence interval [CI]: 91-120) in Group A versus 128 months (CI:117-139) in Group B (P = 0.47, log-rank analysis). On subgroup analysis of Group A, augmented bladders had the poorest mean survival (81 months, CI: 56-106), P = 0.09). The mean estimated patient survival was comparable between Group A and B (109 months, CI: 96-122 versus 139 months, CI: 134-144), P = 0.13). Infective complications (27 episodes vs. 1) and re-admissions (77 vs. 30) were significantly higher in Group A (P = 0.04 and P < 0.01). Clean intermittent catheterization was a risk factor for infections (63% vs. 37%, P = 0.033, odds ratio: 5). CONCLUSIONS: The graft and overall survival was comparable at 3 years in both groups. Infective complications were higher in Group A.

Podocyte Infolding Glomerulopathy (PIG) in a Patient With Undifferentiated Connective Tissue Disease: A Case Report.

Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder. Ultrastructural analysis of the kidney biopsy specimen revealed unusual subepithelial aggregates of microspherules admixed with few microtubules alongside extensive infolding of podocyte foot processes into the underlying GBMs. Characteristic clustering of these microparticles near the invaginated tips of podocyte foot processes in the GBM was observed on transmission electron microscopy. The patient's clinical condition responded favorably to immunosuppressive therapy. The clinical, light microscopic, and diagnostic electron microscopic features of this condition are highlighted in this report in an attempt to contribute some insights into the possible pathogenetic mechanisms of this obscure entity.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre.

AIM: We report findings from a large single centre paediatric renal biopsy cohort in South Asia. METHODS: We analyzed all renal biopsies performed on children aged ≤18 years between 1996 and 2015 at our centre. The clinical characteristics and histological diagnosis pertaining to each case, distribution of renal diseases in children with various clinical presentations, and changes in the pattern of kidney disease during the study period were analyzed. RESULTS: A total of 1740 paediatric kidney biopsies were performed during the study period. The mean age was 12.8 ± 4.9 years (8 months to 18 years) and the male: female ratio was 1.5:1. The most common indication for renal biopsy was nephrotic syndrome (63.2%) followed by acute nephritic syndrome (13%). Minimal change disease was the most common cause of nephrotic syndrome while endocapillary proliferative glomerulonephritis (65.7% infection related), remained the commonest cause of acute nephritic syndrome. IgA nephropathy was the commonest cause of chronic kidney disease. Contrary to trends in European paediatric cohorts, the frequency of lupus nephritis increased over the two decades of the study, while that of endocapillary proliferative glomerulonephritis did not show any appreciable decline. CONCLUSION: This study provides the largest data on biopsy proven renal disease in children from South Asia published till date and highlights important differences in the spectrum and trends of kidney disease compared to data from other regions.

Indian chronic kidney disease study: Design and methods.

AIM: The rate and factors that influence progression of chronic kidney disease (CKD) in developing countries like India are unknown. A pan-country prospective, observational cohort study is needed to address these knowledge gaps. METHODS: The Indian Chronic Kidney Disease (ICKD) study will be a cohort study of approximately 5000 patients with mild to moderate CKD presenting to centres that represent different geographical regions in India. Time to 50% decline in baseline estimated glomerular filtration rate, need of renal replacement therapy or any new cardiovascular disease (CVD) event or death from CVD are the primary end points. VALUE OF STUDY: This study will provide the opportunity to determine risk factors for CKD progression and development of CVD in Indian subjects and perform international comparisons to determine ethnic and geographical differences. A bio-repository will provide a chance to discover biomarkers and explore genetic risk factors.

Pharmacokinetics of concentration-controlled mycophenolate mofetil in proliferative lupus nephritis: an observational cohort study.

BACKGROUND: Mycophenolate mofetil (MMF) has variable pharmacokinetics. This study examines the pharmacokinetic and clinical correlations in proliferative lupus nephritis. METHODS: Thirty-four patients were started on MMF, and the area under the concentration-time curve (AUC) was measured by limited sampling strategies, and dosing was adjusted to achieve an AUC of 30-60 mg·h·L. Twenty-seven patients had at least 2 measurements, and renal response was assessed within 1 year. RESULTS: About 61.8% of patients had mycophenolic acid (MPA) AUC <30 mg·h·L with an empiric starting dose of 30 mg/kg. About 79.4% of patients achieved renal response by 1 year, and the median time to renal response was 111 days. MMF dose per body weight had a weak correlation with the AUC and did not correlate with trough concentrations. The median dose was 1.5 g/d at entry and 2 g/d after dose modification during the induction phase. Trough concentrations had a weak correlation with AUC. Patients with serum albumin ≥35 g/L had a greater chance of having an AUC ≥30 mg·h·L. The between-patient coefficient of variability for dose-normalized AUC was 37.9% at entry and 31% within 1 year, whereas repeated measurements over time in an individual had a good intraclass correlation of 0.78. Infections occurred in 11.8% and toxicities in 5.9%. MPA exposure was not significantly associated with adverse events. Patients with an AUC ≥30 mg·h·L had greater renal response at 1 year. CONCLUSIONS: Lupus nephritis patients induced with concentration-controlled MMF had excellent renal response and fewer adverse events with lower than usual dosing. MPA exposure had high interpatient variability, requiring measurements for personalized dosing, and fewer adverse events. Long-term cost reduction is achievable with lower doses and good renal response in the majority of patients.

The Effect of Intradialytic Aerobic Exercise on Dialysis Parameters and Fatigue in Hemodialysis Patients: A Non-randomized Interventional Study.

Introduction Hemodialysis is the standard treatment for end-stage renal disease. However, patients receiving hemodialysis can become less active as a result of treatment, resulting in the accumulation of waste products. Intradialytic exercise improves the clearance of urea and creatinine by opening up vascular beds. Materials and methods We conducted a non-randomized interventional study to evaluate the effect of intradialytic aerobic exercise on dialysis parameters and fatigue among 295 hemodialysis patients selected through consecutive sampling (control group, n=147; experimental group, n=148) from two tertiary care centers. Baseline data on background variables and pre-test dialysis parameters (e.g., blood urea, creatinine, potassium, and hemoglobin levels) were assessed in both groups. Following connection to the hemodialysis machine, participants in the experimental group engaged in 15 minutes of intradialytic aerobic exercise per two hours of dialysis for a total of eight weeks, besides receiving routine care, compared to those in the control group. Post-test dialysis parameters were assessed for both groups at the end of the eighth week. The collected data were analyzed and tabulated using SPSS (IRB Inc., Armonk, New York). Results Intradialytic exercise led to significant improvements in post-test blood urea, creatinine, and fatigue in the experimental group (p<0.001). However, post-test serum potassium and hemoglobin levels remained relatively unchanged. Conclusion This study demonstrates the benefits of intra-dialytic aerobic exercise as a safe complementary therapy for a large population of dialysis patients, leading to better patient outcomes.

Centrifugal technique of plasma exchange and low-dose steroid to treat very severe alcoholic hepatitis patients: A retrospective analysis.

BACKGROUND: Low-volume plasma exchange (PLEX) and low-dose steroid improve survival in severe alcoholic hepatitis. We aimed to compare one-year survival of very severe alcoholic hepatitis (VSAH) patients treated with centrifugal PLEX (cPLEX), membrane PLEX (mPLEX) or standard medical treatment (SMT). METHODS: We retrospectively analyzed survival in consecutive VSAH patients treated at our department from November 2017 to September 2021. PLEX patients received low-volume PLEX along with low-dose steroid (tab. prednisolone 10 mg or 20 mg daily). To adjust for baseline differences between the three treatment (cPLEX, mPLEX or SMT) groups, propensity score (PS) matching was done. Acute-on-chronic liver failure (ACLF) was defined as per European Association for the Study of the Liver (EASL). The primary study outcome was one-year transplant-free survival of PS-matched VSAH patients treated with cPLEX compared to SMT. RESULTS: Of 101 PLEX-eligible VSAH patients, 30 patients were treated with cPLEX, 21 with mPLEX and 50 with SMT. On comparing 30 PS-matched patients each in the cPLEX group vs. the SMT group, transplant-free survival in the cPLEX group was 86.7% at one month, 70% at three months and 52.4% at one year and in the SMT group was 33.3% at one month, 23.3% at three months and 16.7% at one year with hazard ratio (HR [95% CI]) in favor of the cPLEX group (0.29 [0.15-0.56], p < 0.001). Total 21 patients each (PS-matched) in cPLEX and mPLEX groups were compared and one-year survival was better with cPLEX (0.33 [0.16-0.69], p = 0.001). The sub-group analysis of VSAH (PS-matched cohort) patients with ACLF also showed better survival with cPLEX compared to SMT (0.38 [0.17-0.83], p = 0.003) and compared to mPLEX (0.43 [0.17-0.95], p = 0.03). CONCLUSION: Better one-year transplant-free survival was noted among PS-matched VSAH patients treated with cPLEX (and low-dose steroid) compared to SMT (without steroid).

Profile, Risk Factors, and Outcomes of Asymptomatic Bacteriuria in Kidney Transplant Recipients with Normal Pretransplant Genitourinary Tract: A Single-Center Experience.

Introduction: There is a paucity of studies on asymptomatic bacteriuria (ASB) among kidney transplant recipients (KTR) in developing countries. This study assessed the clinical profile, risk factors, outcomes, and impact of treatment of ASB in KTRs with a normal genitourinary tract. Methods: Consecutive KTRs from 2009 to 2018 with no clinical or radiological evidence of obstructive uropathy were included. Urinary tract infection (UTI) after ASB was defined as occurrence of cystitis, pyelonephritis, or urosepsis, with ASB being the first bacteriuric episode. Results: Seven hundred ten out of 794 patients with median follow up of 47 months were included. The mean age was 35.5 ± 12 years. Eighty-one patients (11.4%) developed ASB at a median of 25 days (IQR 10, 134.5). Fifty-three percent and 4.9% of ASB episodes were extended-spectrum beta-lactamase (ESBL) positive and carbapenem-resistant organisms, respectively. Eighteen patients (32.1%) with early ASB (<3 months) and 5 (20%) with late ASB developed UTI on follow-up. Fifty-five percent of early and 16% of late ASB episodes were treated, with no significant difference observed in the risk of development of UTI when compared to untreated ASB episodes. Conclusion: The incidence of ASB as first bacteriuric episode in our cohort was 11.4%, with there being significant antimicrobial resistance. Female gender, pretransplant UTI, and delayed graft function were independently associated with development of ASB. Treatment of ASB episodes either early or late did not decrease the risk of development of UTI.

On-treatment decline in MELD score predicts one-month transplant-free survival in rodenticidal hepatotoxicity patients treated with low-volume plasma exchange.

BACKGROUND AND AIM: Plasma exchange (PLEX) improves survival in patients with rodenticidal hepatotoxicity. However, predictors of treatment response are unknown. We aimed at assessing predictors of response to PLEX treatment in these patients. METHODS: Patients with rodenticidal hepatotoxicity from 2014 to 2023 managed in our department were included in this study. Kochi criteria (model for end-stage liver disease [MELD] score ≥ 36 or international normalized ratio [INR] ≥ 6 with hepatic encephalopathy [HE]) derived specifically for rodenticidal hepatotoxicity (PubMed IDentifier [PMID]: 26310868) were used to assess need for liver transplantation. We analyzed predictors of survival at one month. ∆Bilirubin, ∆MELD score and ∆INR were calculated as percentage change of the parameter after third PLEX session (or after last PLEX if < 3 PLEX sessions done) from baseline pre-PLEX value. RESULTS: Of 200 patients with rodenticidal hepatotoxicity, 114 patients were treated with low-volume PLEX (PLEX-LV). No patient had liver transplantation. Of 78 patients who fulfilled Kochi criteria, 32 patients were PLEX-LV eligible and underwent PLEX-LV (M: 10; age: 20.5, 7-70 years; median, range; acute liver failure: 24). Twenty-two (69%; acute liver failure: 14) of the 32 patients were alive at one month. Presence of HE (p = 0.03) and ∆MELD (p < 0.001) were significant predictors on univariate analysis, while ∆MELD (aOR = 0.88, 95% CI: 0.79-0.98, p = 0.01) was the only significant independent predictor of one-month transplant-free survival. Area under receiver operating characteristic (ROC) for ∆MELD was 0.93 (95% CI:0.85-1.00) and a decrease of ≥ 20% in MELD score while on PLEX-LV had 90% sensitivity and 90% specificity in predicting one-month survival. CONCLUSIONS: Decline in MELD while on PLEX-LV independently predicted one-month transplant-free survival in rodenticidal hepatotoxicity patients. This may help guide decision on stopping PLEX-LV in patients predicted to respond to treatment and to consider alternate treatment options in non-responders.

Therapeutic potential of urine exosomes derived from rats with diabetic kidney disease.

Kidney disease is prevalent in diabetes. Urinary exosomes (uE) from animal models and patients with Diabetic nephropathy (DN) showed increased levels of miRs with reno-protective potential. We examined whether urinary loss of such miRs is associated with their reduced renal levels in DN patients. We also tested whether injecting uE can leverage kidney disease in rats. In this study (study-1) we performed microarray profiling of miRNA in uE and renal tissues in DN patients and subjects with diabetes without DN (controls). In study-2, diabetes was induced in Wistar rats by Streptozotocin (i.p. 50 mg/kg of body weight). Urinary exosomes were collected at 6th, 7th and 8th weeks, and injected back into the rats (100ug/biweekly, uE-treated n=7) via tail vein on weeks 9 and 10. Equal volume of vehicle was injected in controls (vehicle, n=7). uE from the human and rat showed the presence of exosome-specific proteins by immunoblotting. Microarray profiling revealed a set of 15 miRs having high levels in the uE, while lower in renal biopsies, from DN, compared to controls (n=5-9/group). Bioinformatic analysis also confirmed the Renoprotective potential of these miRs. Taqman qPCR confirmed the opposite regulation of miR-200c-3p and miR-24-3p in paired uE and renal biopsy samples from DN patients (n=15), relative to non-DN controls. A rise in 28 miRs levels, including miR-200c-3p, miR-24-3p, miR-30a-3p and miR-23a-3p were observed in the uE of DN rats, collected between 6th-8th weeks, relative to baseline (before diabetes induction). uE- treated DN rats had significantly reduced urine albumin-to-creatinine ratio, attenuated renal pathology, and lower miR-24-3p target fibrotic/inflammatory genes (TGF-beta, and Collagen IV), relative to vehicle treated DN rats. In uE treated rats, the renal expression of miR-24-3p, miR-30a-3p, let-7a-5p and miR-23a-3p was increased, relative to vehicle control. Patients with diabetic nephropathy had reduced renal levels, while higher uE abundance of miRs with reno-protective potential. Reverting the urinary loss of miRs by injecting uE attenuated renal pathology in diabetic rats.

Treating Parvovirus Triggered Refractory Hemolytic Anemia with Rituximab in Renal Transplant Recipients - A Report of Two Cases.

Parvovirus B19 is a small (26 nm), nonenveloped, single-stranded DNA (5.6-kb) virus. The only known host for parvovirus B19 is humans. Parvovirus B19 is directly cytotoxic to erythroid precursor cells of the colony- and burst-forming units. Human parvovirus B19 is the etiologic agent of erythema infectiosum and chronic pure red cell aplasia in immunocompromised individuals. Acute parvovirus B19 infection should be suspected in immunocompromised patients, who present with reticulocytopenic hemolytic anemia and thrombocytopenia. Intravenous immunoglobulin (IVIg) is the standard treatment for parvovirus-induced cytopenias. We report two cases of postrenal transplant who presented with reticulocytopenic anemia and were found to have parvovirus infection. They did not respond to conventional treatment with intravenous gamma globulin. Both patients were treated with rituximab with which they had improvement in clinical and hematological parameters. There was no previous documentation of using rituximab in the treatment of parvovirus-triggered autoimmune hemolytic anemia postrenal transplant patients. This article illustrates how rituximab will be helpful in this setting, of course, it is a new thought but requires further studies and validation.