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.

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.

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.

Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients.

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft "mesangiolysis" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). "Associated extra-renal GvHD" occurred in 11/19 (57.9%) allogenic recipients. Patients with "associated extra-renal GvHD" had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without "associated extra-renal GvHD" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

Three-Year Clinical Outcomes of the First South Asian Prospective Longitudinal Observational IgA Nephropathy Cohort.

INTRODUCTION: Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgA nephropathy (IgAN) cohort with prespecified objectives, protocolized longitudinal follow-up, and extensive biosample collection. The baseline risk scores predicted high risk of kidney disease progression. METHODS: A total of 195 of 201 patients (97%) completed 3-year follow-up in September 2020. All patients received optimized supportive care, and those at high risk of progression were offered systemic corticosteroids. RESULTS: A total of 76 patients (76 of 193, 39.4%) had rapid progression in 3 years (≥5 ml/min per 1.73 m2 decline in estimated glomerular filtration rate [eGFR] per year). A total of 72 patients (72 of 195, 36.9%) experienced the composite outcome (CO), defined as ≥50% fall in eGFR, eGFR < 15 ml/min per 1.73 m2, commenced kidney replacement therapy or death, in 3 years. At each scheduled follow-up, achievement of proteinuria level < 1 g/d significantly delayed the time to the CO. The receiver operating characteristic curve of average annual decline in eGFR ≥ 5 ml/min per 1.73 m2 had 86% sensitivity and 89% specificity for CO in 3 years and had good discrimination from 1 year onwards (area under the curve 0.8, SE 0.04, 95% CI 0.7-0.9, P < 0.0001). The significant predictors of CO by Cox proportional-hazards model were as follows: baseline MEST-T2 score (hazard ratio [HR] 3.3, 95% CI 1.7-6.5, P < 0.001), along with 24-hour urine protein level ≥ 1 g/d (HR 2.1, 95% CI 1.1-3.9, P = 0.02), eGFR < 60 ml/min per 1.73 m2 (HR 2.9, 95% CI 1.1-7.6, P = 0.03), and rate of eGFR decline ≥ 5 ml/min per 1.73 m2/yr (HR 2.7, 95% CI 1.6-4.8, P < 0.001) all measured at 6 months. Mortality was 11 of 195 (5.6%). CONCLUSION: We identified longitudinal clinical variables measured at 6 months and ≥5 ml/min per 1.73 m2 annual fall in eGFR after kidney biopsy as important predictors for composite outcome in addition to baseline histology.

Impact of the Lockdown on Patients Receiving Maintenance Hemodialysis at a Tertiary Care Facility in Southern India - A Mixed-methods Approach.

Aims: The mass quarantine measures adopted to control the COVID-19 pandemic greatly impacted the lives of patients on haemodialysis in India. We used a mixed methods approach to study its effect on dialysis outcomes and the lived experience of haemodialysis patients during the lockdown. Methods: Quantitative data was collected from 141 subjects using a structured proforma to determine the impact of the lockdown on dialysis outcomes and travel expenses. Qualitative data collected through in-depth interviews with 9 patients by purposive sampling were recorded and transcribed to explore the lived experience of haemodialysis patients during lockdown. The cohort was followed up till October 31st 2020 for incidence of COVID-19, deaths, and dropouts. Results: The median increase in per day travel expense was 25%. Due to decrease in dialysis frequency, patients previously on thrice weekly haemodialysis experienced significant increase in pre-dialysis systolic blood pressure (P = 0.005) compared to those on twice weekly haemodialysis. Between March 25th and July 15th 2020, 12 patients (8.5%) required emergency dialysis sessions, and 4 patients (2.8%) required admissions for hypertensive emergencies. Four main themes emerged from thematic analysis of transcribed interviews: Travel inconveniences, uncertainty resulting in anxiety, financial burden and frequency change in dialysis leading to worsening of symptoms. Twenty-two patients (15.6%) were diagnosed with COVID-19, the first case diagnosed 33 days after the first 'unlock' phase. Conclusion: The lockdown was successful in delaying infection transmission but had unintended physical and psychosocial effects on haemodialysis patients.

Latency, Anti-Bacterial Resistance Pattern, and Bacterial Infection-Related Glomerulonephritis.

BACKGROUND AND OBJECTIVES: Bacterial infection-related GN occurs concurrent to or after known or unknown infections. It is important to understand the clinical implications of the bacterial isolates, antimicrobial resistance patterns, and effect of latency-based classification on kidney and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 501 consecutive adults diagnosed with bacterial infection-related GN between 2005 and 2017 were included from a biopsy registry of 15,545 patients at a single center in South India, and follow-up data were collected from electronic medical records until December 2019. Latency was defined as time between resolution of infection and onset of GN, which was classified as parainfectious, peri-infectious, or postinfectious GN. Longitudinal kidney and patient outcomes were studied. RESULTS: The mean age of the cohort was 40 (± 15) years, 6% were above 65 years, and 330 (66%) were men. Diabetes was present in 93 (19%) patients. Seventy percent (353 of 501) of patients had known infections, with the median latent period for parainfectious (115 of 353, 33%), peri-infectious (97 of 353, 27%), and postinfectious (141 of 353, 40%) GN being 0, 5 (4-7), and 15 (10-31) days, respectively. The most common predisposing organism was Streptococcus pyogenes (137 of 353, 39%). Drug-resistant nonstreptococcal bacteria were methicillin-resistant Staphylococcus aureus (25%, four of 16), extended-spectrum ß-lactamases (20%, 12 of 59), and carbapenem-resistant organisms (10%, six of 59). Twenty of 22 (91%) of the drug-resistant organisms were isolated from the parainfectious group. The most common site of infection was skin in peri- (23 of 97, 24%) and postinfectious GN (61 of 141, 43%), and urinary tract in parainfectious GN (35 of 115, 30%). Of 321 patients with >3 months of follow-up, 48 (15%) developed kidney failure over a median period of 10 (2-37) months and 14 (4%) died. Parainfectious GN, eGFR<30 ml/min per 1.73 m2, moderate-to-severe interstitial fibrosis and tubular atrophy, and nontreatment with renin-angiotensin system blockers were significant risk factors for progression to kidney failure by a Cox proportional-hazards model. CONCLUSIONS: Along with clinical and histologic predictors, parainfectious GN caused predominantly by nonstreptococcal and drug-resistant bacterial infections was associated with poor kidney prognosis.

Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients.

With low rates of rejection with current immunosuppression consisting of steroids, mycophenolic acid and tacrolimus, the question arises whether induction offers any additional benefit in low-risk renal transplant recipients. This study evaluated outcomes with and without induction in low-risk renal transplant recipients. A prospective observational study in which 100 low-risk renal transplant recipients were included and divided into two groups - one that received induction (IND) and another that did not (NO IND). They were followed for 1.5 years. Three endpoints were compared - efficacy of induction, patient and graft survival, and adverse effects. Incidence of rejection in early posttransplant period did not differ (4% NO IND vs. 6% IND; P = 0.171). Rejection as cause of late graft dysfunction was seen in 16% in IND vs. 20% NO IND; (P = 0.603). No difference in serum creatinine at end of 1.5 years was seen. Graft survival was also similar. Relapsing and recurrent urinary tract infections (46% IND vs. 16% NO IND; P = 0.09), hospitalization requiring infections (76%IND vs. 64% NO IND; P = 0.119 NS) were more common in IND. Cytomegalovirus infection affected only IND (6% vs. none; P = 0.07). Patient survival at 1.5 years was comparable (94% IND vs. 96% NO IND; P = 0.646). The study showed comparable results between IND and NO IND with however an increased incidence of infections and hospitalizations in the IND group. The use of induction may be avoided in low-risk renal transplant recipients.

Blind Bedside Peritoneal Dialysis Catheter Repositioning: An Innovative Technique.

Catheter malfunction in peritoneal dialysis (PD) patients may lead to technique failure. Surgical repositioning is sometimes required for resumption of PD and is associated with additional costs of procedure and hospitalization. Meanwhile, patients may need hemodialysis via a temporary vascular catheter with increasing costs and risk of catheter-associated bacteremia. We describe an innovative technique of blind bedside PD catheter repositioning as a possible alternative to surgical repositioning when there is catheter malfunction. In 29 patients over a period of 3 years, we attempted blind bedside PD catheter repositioning with immediate successful inflow and outflow in all of them after repositioning. At 1 month, 21 (72.4%) patients had good catheter function and at 6 months, 19 (65.5%) patients were continuing successful PD. This bedside innovative procedure allowed for catheter salvage without constructing a new exit site or tunnel and without the requirement of a break-in period. The benefits to the patient in terms of cost and shortened hospital stay make it ideal for resource-poor settings. We suggest that this innovative technique be attempted before resorting to the open surgical method of PD catheter repositioning.

Crescentic glomerulonephritis: what's different in South Asia? A single center observational cohort study.

Background: The spectrum and outcomes of crescentic glomerulonephritis (Cr.GN) in South Asia is vastly different from that reported worldwide and there is a paucity of information. The aim of the study was to study the demography, clinical presentation, histology and predictors of longitudinal outcomes of Cr.GN in this population. Methods: An observational cohort study of renal biopsies was performed in the largest tertiary center in South India over a period of 10 years (January 2006 to December 2015) with ≥50% crescents on renal histology indicating Cr.GN. Results: A total of 8645 kidney biopsies were done; 200 (2.31%) were Cr.GN. Patients were categorized into three etiological groups: anti-glomerular basement membrane (type I), immune complex (type II), and pauci-immune (type III). Type II was the most common (96, 46.5%), followed by type III (73, 38%) and type I (31, 15.5%). Female preponderance was seen across all types. About half of all patients presented with recent onset hypertension. Type II had the highest median proteinuria (4.2 (2.1-6) g/day, p=0.06) and the median estimated glomerular filtration rate was lowest in type I (5 (4-8) ml/min/1.73m 2, p<0.001). Among type III, anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis was seen only in ~50% of patients. Nearly one third of patients with type I were also positive for ANCA making them 'double positive'. Acute glomerular insults like tuft necrosis and chronic changes as evidenced by moderate to severe interstitial fibrosis, was a predominant feature of type I. Conclusions: ANCA-negative pauci-immune vasculitis, as well as double positive Cr.GN, are reported for the first time in South-Asia. Renal survival was significantly worse in type I/III compared to type II. Types I/III, moderate to severe interstitial fibrosis and tubular atrophy, presence of oliguria/anuria and increasing percentage of crescents in renal biopsy were significant predictors of end stage kidney disease in our cohort.