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.

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.

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.

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.

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.

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.

Does Hemodialysis Need to be Initiated to Improve Platelet Function in CKD G5 Patients? A Pilot Prospective, Observational Cohort Study.

INTRODUCTION: We previously showed that patients with chronic kidney disease (CKD) Stage G4-5 have normal bleeding times. This made us question whether hemodialysis (HD) initiation was really necessary solely to improve platelet function. METHODS: In this prospective observational study, two 5 ml citrated blood samples and one 2 ml EDTA blood sample were collected from incident HD patients fulfilling inclusion criteria prior to HD initiation (baseline sample) and after three sessions of short duration, low flow, counter-current HD. In each instance, one sample was used to perform Collagen adenosine diphosphate closure time (CADPCT) using the Platelet function analyzer (PFA 200, normal range 68-142 seconds) and the second for light transmission aggregometry (LTA) with ADP as agonist (normal ≥50%). RESULTS: This study included 20 patients between October 2017 and February 2019. Overall, and in the subgroup with normal baseline CADPCT or LTA, there was no statistically significant improvement after HD. However, of the 30% of patients who had an abnormal baseline CADPCT, 50% attained a normal value after three HD sessions, and the overall reduction in CADPCT in this group was statistically significant (P = 0.02). Of those with a baseline normal CADPCT, 21% developed abnormal prolongation post HD. CONCLUSION: HD for the sole purpose of improving platelet function is only of benefit in the subgroup of patients with an abnormal CADPCT at baseline, with close to 50% normalizing their platelet function after three sessions of low flow, short duration, counter-current HD.

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 .

Epidemiology, baseline characteristics and risk of progression in 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 IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. METHODS: 201 incident adults with kidney biopsy-proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median follow-up of 30 months (interquartile range [IQR] 16-39). RESULTS: The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite <10 months of lead time to kidney biopsy. The GRACE-IgANI kidney biopsy data demonstrated a disproportionate absence of active glomerular lesions and overrepresentation of segmental sclerosing lesions and tubulointerstitial fibrosis at presentation, often coexistent with relatively well-preserved estimated glomerular filtration rate (eGFR) and low levels of proteinuria, especially in males. Baseline risk of progression was calculated for each evaluable patient using 2 different risk prediction tools. The median 5-year absolute risk of end-stage kidney disease (ESKD) was 19.8% (IQR 2.7-57.4) and median 5-year risk of progression to the combined endpoint of 50% decline in eGFR or ESKD was 35.5% using the 2 tools. CONCLUSIONS: The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype.

Chyluria with massive proteinuria: Do not reach for the biopsy gun!

We report on a patient presenting with persistent chyluria due to filariasis, whose clinical course was complicated by massive proteinuria and severe hypoalbuminemia. Treatment with dietary manipulation, antifilarials, and sclerotherapy resulted in successful reversal of the above abnormalities. It has been reported that chyluria is not associated with massive proteinuria, or that even in cases of massive proteinuria, hypoalbuminemia is not seen and implies a glomerular pathology. We argue that chyluria is always associated with proteinuria, which may be massive, and does not warrant a kidney biopsy unless proteinuria persists despite resolution of chyluria.

Fibrillary glomerulonephritis in a human immunodeficiency virus-positive, hepatitis C-negative Indian patient: Expanding the profile of renal involvement in human immunodeficiency virus infection.

Highly active anti retroviral therapy (HAART) has dramatically improved life expectancy of human immunodeficiency virus (HIV) infected patients, converting HIV infection into a chronic illness with associated changes in its attendant renal complications. The past two decades have witnessed a decrease in the prevalence of HIV associated nephropathy (HIVAN), traditionally considered to be the hall mark of renal involvement in HIV infection. Simultaneously a host of other glomerular and tubulo-interstitial diseases have emerged, expanding the spectrum of HIV associated renal diseases, predominant among which is HIV associated immune complex mediated kidney diseases (HIVICK). Of the diverse glomerular diseases constituting HIVICK, fibrillary glomerulonephritis (FGN) remains a rarity, with only two existing reports to date, confined to patients co-infected with Hepatitis C virus (HCV). The pathogenetic role of HIV in these patients remains under a cloud because of previously well established association of HCV infection and FGN. We report a case of FGN in a HIV seropositive, HCV negative Indian patient, highlighting the diagnostic electron microscopy (EM) findings of FGN and strengthening the causal association of HIV with FGN. In view of increasing heterogeneity of renal complications in HIV infection, the diagnostic utility of a comprehensive renal biopsy evaluation inclusive of EM is emphasized for appropriate selection of treatment modalities.

Endovascular management of a large retroperitoneal haemorrhage resulting from dual testicular and intra-renal arterial injury after renal biopsy.

Percutaneous renal biopsy is a minimally invasive procedure in the work up of a chronic kidney disease patient. However, it is not free from the complications. Hematuria and abdominal haemorrhage due to intra-renal artery injury are the common complications. We report and discuss the management of a rare case of retroperitoneal haemorrhage resulting from dual arterial injury involving left testicular artery and intra-renal artery.

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.

An uncommon cause of postpartum renal failure--bilateral emphysematous pyelonephritis.

Peripartum acute renal failure is an important complication related to pregnancy leading to significant morbidity and mortality. Emphysematous pyelonephritis (EPN) is a severe necrotizing infection of the renal parenchyma, with formation of gas within the collecting system, renal parenchyma, or perirenal tissues. EPN is common in persons with diabetes or urinary tract obstruction. Herein we report a case of bilateral emphysematous pyelonephritis in a postpartum lady who had no evidence of diabetes or urinary tract obstruction. Management of this condition has traditionally been aggressive, and surgery has been considered mandatory. Our patient was managed successfully with antibiotics and supportive measures alone.