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.

Predictors of Short-Term Outcomes in Living Donor Renal Allograft Recipients: A Prospective Study From a Tertiary Care Center in North India.

Background Renal transplantation is the optimal treatment for patients of all ages with end-stage kidney disease. The long-term outcomes of renal transplantation are assessed by graft and patient survival rates. These outcomes are, in turn, influenced by post-transplant events such as delayed graft function, rejections, post-transplant infections, and post-transplant diabetes mellitus (PTDM). Each of these short-term outcomes is, in turn, determined by the interplay of various factors in the pre-, peri-, and post-transplant period. This prospective study was designed to understand the factors affecting short-term outcomes in living donor transplantation and their effect on graft and patient survival. Methodology A total of 86 patients underwent live donor renal transplantation between January 1, 2015, and March 31, 2016, at a tertiary care hospital in north India. Of these, five were lost to follow-up, and the remaining 81 patients were prospectively followed up to December 31, 2017. Results The majority of the recipients were males (91%) and the donors were females (74%). Spousal and related donors comprised 49% and 51% of donations, respectively. The mean estimated glomerular filtration rate (eGFR) of donors was 98 ± 9.2 mL/minute/1.73m². Induction therapy with basiliximab was given to 21/81 (26%) recipients. The majority of recipients (68/81, 84%) received triple-drug immunosuppression with prednisolone, tacrolimus, and mycophenolate mofetil. Delayed graft function (DGF) occurred in 4/81 (4.9%) cases. Biopsy-proven acute rejections (BPARs) occurred in 15/81 (18.5%) cases, two-thirds of which were acute antibody-mediated rejections (ABMRs). During the follow-up period, 50 episodes of infections occurred in 35/81 (43.2%) recipients, with the most common being urinary tract infection (23/81, 28.5%). PTDM was diagnosed in 22/81 (27.2%) patients beyond six weeks of transplant. On multivariate logistic regression analysis, the most significant predictor of DGF was acute rejections and vice versa. Acute rejections also predicted the occurrence of post-transplant infections. Pre-transplant hepatitis C virus (HCV) infection and cyclosporine-based therapy were significant predictors of PTDM. At the six-month follow-up, 10/81 (12.3%) patients developed graft dysfunction. The predictors of graft dysfunction at six months were recipients of related donors and rural patients. One-year graft survival, death-censored graft survival, and patient survival rates were 85.2%, 92.6%, and 91.3%, respectively. The most common cause of death was post-transplant infections (5/7, 71.4%) of which the majority (4/5, 80%) were fungal infections. On multivariate logistic regression analysis, the most significant predictor of graft loss and patient loss was low pre-transplant donor eGFR and PTDM, respectively. Conclusions Graft and patient survival in living donor kidney transplantation are influenced by a multitude of interdependent factors during the pre-transplant (donor eGFR, type of donor, socioeconomic status, HCV infection in recipient, type of immunosuppression) and the post-transplant (DGF, rejections, infections, and PTDM) period.

When to Suspect Non-diabetic Kidney Disease in a Diabetic Patient?

The diagnosis of non-diabetic kidney disease (NDKD) in a diabetic patient has significant therapeutic and prognostic implications. There are certain proven clinical predictors of NDKD, which, when present in an appropriate clinical setting, would warrant a kidney biopsy. Herein, we describe four cases of NDKD diagnosed in rather unusual clinical settings, which add to the list of clinical predictors of NDKD. The first case was a "parainfectious glomerulonephritis" diagnosed in a 50-year-old diabetic woman who presented with persistent renal dysfunction despite successful treatment of urinary tract infection. The second case was "membranous nephropathy" diagnosed in a 43-year-old man with long-standing type 1 diabetes, which was associated with other microvascular complications. In this case, the only predictor was disproportionately low serum albumin. The third case was "amyloid light chain (AL) amyloidosis" diagnosed in an elderly diabetic who presented with progressive anasarca over six months. In this case, the only clinical predictor was a disassociation observed between urine dipstick and 24-hour protein estimation. In the fourth case, an elderly diabetic woman without underlying diabetic retinopathy presented with sudden onset nephrotic syndrome. A kidney biopsy was suggestive of diffuse nodular glomerulosclerosis. Immunofluorescence and electron microscopic evaluation were diagnostic of "gamma heavy chain deposition disease." In all four cases, diagnosis of NDKD led to major therapeutic changes and attainment of renal remission. We have extensively reviewed all major biopsy cohorts of NDKD and have formulated an approach to the diagnosis of NDKD.

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.

Difficult cannulation of hemodialysis arteriovenous fistula - Role of imaging in access management (DICAF STUDY).

BACKGROUND: Difficulty in cannulation of arteriovenous fistula (AVF) can lead to inadequate dialysis, transient to permanent loss of access and increases dependency on bridging catheters. This study aimed to analyze the causes for difficult fistula cannulation, using various imaging modalities. METHODOLOGY: This was a retrospective single-center observational study conducted between October 2017 and June 2018. Patients whose fistulae were difficult to cannulate were initially evaluated by physical examination followed by doppler ultrasonography or/and fistulogram as necessary. The patients were divided into two groups that is, primary difficult cannulation (within first three months of creation of fistula) or secondary difficult cannulation (after three months). RESULTS: We encountered difficult cannulation in 43 patients. About 60% were primary difficult cannulations. Most common causes for difficulty in cannulation were cannulation zone (CZ) stenosis (23.3%), immature fistula (20.9%), outflow stenosis (18.6%), inflow stenosis (11.6%), anatomical abnormalities (11.6%), outflow plus CZ stenosis (9.3%) and inflow plus CZ stenosis (4.7%). Among patients with primary difficult cannulation, immature fistula (34.6%) was the most common cause, whereas CZ stenosis (47.1%) was the most common etiology for secondary difficult cannulation. Edema leading to difficult cannulation was found in 12 patients (27.9%), all of which was due to central vein stenosis. Cannulation resulted in hematoma, fistula thrombosis, failure of fistula and pseudoaneurysm in 83.7%, 27.9%, 16.3%, and 2.3% of cases respectively. Bridging temporary dialysis catheter placement was required in 67.4% patients. Ultrasound doppler had lower diagnostic value when compared to fistulogram (71.4% vs 93.9%, p = 0.014). CONCLUSION: Difficulty in cannulating the arteriovenous fistula is a common problem in hemodialysis patients. We suggest that patients whose fistulae are difficult to cannulate should undergo early radiological evaluation to decrease catheter dependency and access failure.

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.

Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI- Glomerular Research And Clinical Experiments- Ig A Nephropathy in Indians-cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.