Divergent manifestations and outcomes of diffuse crescentic immunoglobulin A nephropathy and pauci-immune crescentic glomerulonephritis on long-term.

BACKGROUND: Diffuse crescentic IgAN (CIgAN) is an uncommon phenotype of IgAN, which presents as rapidly progressive renal failure, similar to patients with pauci-immune crescentic glomerulonephritis(PCGN). There are limited data on outcomes comparisons between the two. METHODS: In this single-center, retrospective cohort study, we compared the clinical features, pathological presentation, and renal outcomes of 52 patients with CIgAN and 42 patients with renal-limited PCGN from January 2007 to December 2019. RESULTS: The CIgAN patients were younger (30.5 ± 13.8 years) than PCGN patients (46.1 ± 11.8 years) (P = 0.001). The CIgAN patients had a higher prevalence of hypertension (86.5% Vs. 41.3%, P = 0.001); and degree of proteinuria (4.2 ± 2.7 g/24 h Vs. 2.3 ± 1.16 g/24 h; P = 0.001) than PCGN patients. The chronicity in terms of global glomerulosclerosis, interstitial fibrosis, and tubular atrophy was higher in the CIgAN group than in the PCGN group. The remission rate with immunosuppression was significantly higher in the PCGN group than in the CIgAN group (P = 0.016). The end-stage renal disease (ESRD) or death within 1 year of diagnosis was significantly more in the CIgAN group (62.3% Vs. 39.1%) than PCGNgroup. For patients who were dialysis-dependent at presentation, the primary outcome of ESRD or death within one year was seen in 90.9% of patients of CIgAN and 44.1% in the PCGN group (P = 0.001). The long-term death non-censored renal survival is poor in the CIgAN group than in PCGN patients. However, patient survival is poor in PCGN patients. CONCLUSION: CIgAN is a different form of RPGN compared to PCGN and carries a poor prognosis despite similar immunosuppressive therapy in the long term.

Rapidly Progressive Renal Failure in Type 2 Diabetic versus Non-diabetic Patients: Changing Trends, Natural History, and Outcome in an Indian Tertiary Care Center.

Rapidly progressive renal failure (RPRF) is not typical of diabetic nephropathy and suggests non-diabetic kidney disease (NDKD). We conducted an analysis of the data of RPRF patients (28 diabetic and 88 non-diabetic patients) with doubled creatinine over 2 weeks to 3 months and/or presented with >4 mg serum creatinine without prior renal disease to ascertain the types of lesions and compare the patients' histopathology. The primary outcome was dependence on dialysis at 1 year. Anti-neutrophilic cytoplasmic antibody-associated pauci-immune glomerulonephritis was the most common cause of RPRF in both groups. No particular lesion was more frequent in either group. Dependence on dialysis at 1 year was similar in both groups and was associated with dependence on dialysis at presentation but not diabetes. Crescentic glomerulonephritis was the most common in non-diabetic patients (57.9 vs. 25%, P = 0.002), and acute tubular necrosis (ATN) was seen in diabetic patients (21.4 vs. 11.4%, P = 0.179). Both factors were associated with adverse renal outcomes. Diffuse global glomerulosclerosis at presentation suggested a poor outcome in both groups. Diabetic nephropathy was seen in 14.29%, and its presence did not affect the outcome. The etiology of RPRF in diabetic patients has changed and is similar to that in non-diabetic patients, with no specific lesions predominating. Diabetic nephropathy does not alter the outcome for those with RPRF. Diffuse global glomerulosclerosis, being on dialysis at presentation, and ATN in a diabetic patient indicate a poor outcome and need close follow-up. Diabetic retinopathy should not prevent us from investigating for NDKD.

Impact of Kidney Donation on Pregnancy Outcomes: A Retrospective Analysis.

Introduction: Recent data suggest a risk of gestational hypertension, proteinuria and pre-eclampsia among pregnancies after kidney donation. Methods: This retrospective study among females who donated kidneys (1997-2017) at a tertiary renal transplant center in Northern India assessed the maternal and fetal outcomes of their pregnancy. Data of participants were collected using pre-tested semi structured questionnaire. Results: In total, 925 female kidney donors (1332 pregnancies) in the pre-donation group and 45 females (48 pregnancies) in the post donation period were included. The mean age of first pregnancy, weight (kg) gain, proportion of history of pre-natal check-up, institutional delivery, and history of unrelated donation was statically significant among the post-donation group. The proportion of pre-eclampsia, gestational hypertension, gestational diabetes, and post-partum hemorrhage was insignificantly higher among the post-donation group with higher preterm birth with low-birth-weight babies. Proteinuria (P < 0.05) was significantly higher among post donation pregnancies. In multivariate analysis, cesarean delivery and low birth weight (<2500 g) were common among the post-donation pregnancy group. Conclusions: The study demonstrated no significant risk to maternal outcomes butan increased risk to fetal outcomes in terms of prematurity and low birth weight among the post-donation pregnancy group.

Risk of tuberculosis among renal transplant recipients receiving rituximab therapy.

BACKGROUND: Rituximab is an anti-CD 20 agent used widely in renal transplant recipients. Its use is associated with various infections; however, its association with tuberculosis (TB) is not well established and has not been studied in post renal transplantation patients. METHODS: This is a single-center, retrospective analysis of 56 renal transplant recipients who received rituximab as a part of desensitization protocol or as rescue therapy for rejections and 287 post-renal transplant patients who did not receive rituximab during the study period from January 2013 to June 2017. The association between use of rituximab and occurance of TB was studied. Other factors associated with TB were also investigated. RESULTS: Baseline characteristics were similar in both the groups. Mean time for occurrence of TB was 18.4 ± 10.6 months after renal transplantation. Rituximab use was not significantly associated with TB or any other infection. Higher number of rejection episodes (60% vs. 32.72%, p = .029) was the only factor associated with greater incidence of TB. However, no specific type of rejection was associated with TB. Use of plasmapheresis in post-transplant period for treatment of humoral rejections was associated with significantly higher incidence of TB (33.33% vs. 13.41%, p = .031); however, when pre-transplant plasmapheresis was also considered, there was no significant difference. The choice of induction agent was not associated with higher incidence of TB. CONCLUSION: Use of rituximab is not associated with higher incidence of TB when compared to other immunosuppressive agents. Routine screening and prophylaxis may not be advisable, especially in a country like India with high prevalence of TB, as it will further delay transplantation and may adversely affect the outcome of the patients.

Impact of Early versus Late Referral to Nephrologists on Outcomes of Chronic Kidney Disease Patients in Northern India.

Background: CKD patients are often asymptomatic in the early stages and referred late to nephrologists. Late referred patients carry a poor prognosis. There is a lack of data on outcomes associated with referral patterns in CKD patients from northern India. Methods: In this observational cohort study, all CKD patients who visited the nephrology OPD of the institute between Nov 1, 2018, and Dec 31, 2020, were classified as early referral (ER) if their first encounter with a nephrologist occurred more than one year before initiation of dialysis and education about dialysis (from a nurse or nephrologist). The remaining others were considered late referrals (LRs). The outcomes impact of early and late referrals was analyzed. Results: A total of 992 (male 656) CKD patients (ER, n = 475 and LR, n = 517) were enrolled. Patients referred early were older and diabetic and had higher BMI, better education, occupation, and socioeconomic status as compared to those referred late. The mean eGFR at first contact with the nephrologist was (25.4 ± 11.5 ml/min) in ER and 9.6 ± 5.7 ml/min in the LR group and had a higher comorbidity score. The CKD-MBD parameters, hemoglobin, and nutritional parameters were worse in LR. Only a few patients had AVF, and the majority required emergency dialysis in the LR group. A total of 91 (9.2%) patients died, 17 (1.7% ER and 74 (7.5%) patients in the LR group patients. There was significantly lower survival at 6 months (ER 97.1% vs. LR 89.7%), 12 months (ER 96.4% vs. LR 85.7%), 18 months (ER 96.4% vs. LR 85.7%), and 24 months (ER 96.4% vs. LR 85.7%) in late referral group as compared to early referral group (P=0.005). Conclusions: LR to nephrologists has the risk of the emergency start of dialysis with temporary vascular access and had a higher risk of mortality. The timely referral to the nephrologist in the predialysis stage is associated with better survival and reduced mortality.

Midterm eGFR Predicts Pregnancy Outcomes: An Observational Study.

INTRODUCTION: The hemodynamic adjustments during pregnancy play a pivotal role in sustaining the gestation, however, its clinical connotation on midterm renal hyperfiltration and its consequence on maternal and fetal outcomes need a greater appraisal. The present retrospective study looked into the midterm estimated glomerular filtration rate (eGFR) among pregnant females without overt pieces of evidence of chronic kidney disease (CKD) as a surrogate marker for midterm hyperfiltration and its implication on maternal and fetal outcomes. MATERIALS AND METHODS: All pregnancies among females aged 18-50 years with available pregestational baseline serum creatinine were included in the study. Maternal renal hyperfiltration was expressed as the highest eGFR, using the creatinine clearance method. Its association with adverse maternal and fetal outcomes was assessed. RESULTS: A total of 1,045 pregnancies were assessed during the study. According to midterm eGFR, among them, 65% of pregnancies showed midterm eGFR between 120 and 150, however, 4.3% of pregnancies had values more than 150 mL/min per 1.73 m2 . The risk of poor pregnancy outcome was observed for eGFR levels below and above the reference level of 120-150 mL/min per 1.73 m2 (1.97 for values ≥150 mL/min per 1.73 m2 , and 1.72 for 90-120 mL/min per 1.73 m2 ). Pregnancies with eGFR between 60 and 90 mL/min per 1.73 m2 had odds ratios (ORs) of 5.64. CONCLUSION: A distinctive relationship was observed between the midterm eGFR and adverse pregnancy outcomes with the best outcomes for midterm eGFR levels between 120 and 150 mL/min per 1.73 m2 . Despite no apparent functional renal deterioration, a poor maternal hyperfiltration response may play a crucial impact on poor pregnancy outcomes.

Feto-maternal and renal outcomes of nephrotic syndrome in pregnancy.

Proteinuria can range from subnephrotic to nephrotic amounts during pregnancy, though nephrotic syndrome (NS) is rare (0.012%-0.025%). Without a renal biopsy, this distinction may be difficult at times. The objective of our study was assessing about renal and feto-maternal outcomes of these patients. This study was done in a tertiary-care hospital in north India from 2010 to 2019. We included all pregnant women with nephrotic-range proteinuria, with no signs or symptoms suggestive of pre-eclampsia. We studied their treatment modalities, renal, maternal, and fetal outcomes. Eighteen eligible pregnant women diagnosed with NS with no features suggestive of pre-eclampsia or associated comorbidities were included. The gestational age of presentation was 23.2 ± 1.36 weeks. The average proteinuria was 4.38 ± 0.76 g/day. The patients were managed conservatively without kidney biopsy. About 16.7% of pregnancies had worsening of hypertension and acute kidney injury which recovered after delivery. Anasarca was troublesome for four patients requiring fresh-frozen plasma infusion. All were managed conservatively; however, five patients were started on empirical immunosuppression, all five with steroids, while two required the addition of calcineurin inhibitors as well. All had live births, but 25.7% each had preterm and intrauterine growth restriction while one required neonatal intensive care unit admission. The degree of proteinuria had an impact on maternal and fetal outcomes, especially on risk to pre-eclampsia. NS during pregnancy needs evaluation and counseling. Majority of them can be managed conservatively yet specific therapies can safely be tried among symptomatic ones. Despite good outcomes, a sizeable risk to maternal and fetal complications can occur.

Red herrings in crossmatching kidneys for transplant.

Crossmatching of prospective renal transplant donors against recipients is a mandatory component of the transplant workup, being performed for over 40 years now. Allografting patients with human leukocyte antigens which are recognized by preformed antibodies constitutes the main cause of hyperacute or acute rejections. The existence of these donor-specific anti-human leukocyte antigen antibodies (DSAs) is regarded as a contraindication for graft trans-plantation, both cadaveric and live kidney. We present two unusual cases in which both complement-dependent cytotoxicity crossmatch and DSA by Luminex were falsely positive due to autoimmune and infectious causes, but single-antigen bead assay showed these antibodies to be against nondonor antigens. After treating their basic disease, thought to be responsible for false-positive DSA, these patients became DSA negative and underwent transplantation with an uneventful posttransplant period. Our aim through these examples is to highlight the problem of false-positive crossmatch in potential renal allograft transplant recipients. Further, we propose antigenic determination of donor-specific antibodies in such patients where we suspect the immune system to be chronically activated to pick up false-positive cases and therefore increase the donor pool without compromising the transplant outcome.

Acute cortical necrosis in pregnancy still an important cause for end-stage renal disease in developing countries.

Renal cortical necrosis (RCN) is a serious complication of acute kidney injury (AKI) and pregnancy is a clinical state closely associated with it with poor renal outcomes. The incidence is much higher in obstetrical AKI compared to other causes of RCN. Despite better medical care facilities available, this continues to be an important cause of morbidity and mortality in developing countries. This is a retrospective analysis among all pregnant females presenting with AKI from January 1999 to December 2014 at a tertiary care center in the northern part of India. We looked for the incidence of obstetrical-related RCN in our renal biopsies performed in the last 15 years and to evaluate precipitating factors responsible for RCN. RCN constituted 8.3% of pregnancy-related AKI cases in our institution. The overall incidence has been declining which was 9.09% from 1999 to 2008 to 7.8% from 2009 to 2014. The patient's median age was 29.3 ± 5.2 years. The average time to presentation from the day of delivery was 8.7 ±2.1 days. The mortality was observed in 11.7% of them with sepsis and multiorgan dysfunction present in all of them. The most common etiology for RCN was found to be septic abortion and puerperal sepsis accounting for - 15.3% each. Postpartum hemorrhage was a cause in 9.09% of patients. The most important cause of RCN was postpartum thrombotic microangiopathy which was observed in 48.7% of patients. Kidney biopsy was helpful in diagnosis in 31 patients while computed tomography scan abdomen alone helped in diagnosis in five patients. Patchy cortical necrosis in histology was seen in 35.4% of patients and morbidity in terms of prolonged hospitalization was seen in 22.7% while dialysis dependency in 61.5% of the study population. In conclusion, strategies need to be implemented in reducing the preventable causes for RCN which is not only catastrophic in terms of renal outcomes but also for social and psychological perspectives as well.

Outcome of renal transplant recipients with cytomegalovirus and BK polyomavirus co-infection nephropathy.

Reactivation of cytomegalovirus (CMV) and BK polyomavirus (BKV) can result in virus-associated tubulointerstitial nephritis in renal allografts. All those renal biopsies reported as viral cytopathic were isolated and examined by two independent renal histopathologists from our institute and classified as CMV, BKV, and CMV-BKV coinfection-associated viral cytopathic changes with confirmation through polymerase chain reaction technology in either serum or urine or both. All twenty patients were categorized as 10 in CMV, four in BKV, and six were in CMV-BKV coinfection. One patient each had received antithymocyte globulin and basiliximab as induction all patients received triple-drug immunosuppression. The mean graft survival was 69, 61, and 59 months in CMV, BKV, and CMV-BKV coinfection group, respectively. At the end of the study period, 10 (50%) patients died. 1-, 3-and 5-year patient survival was 94%, 88% and 76% among CMV group, 75%, 75% and 50% in BKV group, and 96%, 83% and 62%, in CMV-BKV coinfection group (P = 0.157). CMV and BK virus are not so common infections in postrenal transplant patients yet an important cause of graft dysfunction. Coinfection did not pose an increased risk for acute rejection or patients and death-censored and uncensored graft survival among compared groups.

Early versus late institution of plasma exchange therapy in pregnancy induced thrombotic microangiopathy and its effects on clinical outcomes-A case series.

PURPOSE: To look for incidence of pregnancy associated TMA, clinical presentation and impact of early diagnosis and institution of plasma exchange on overall renal outcomes METHODS: -This is a retrospective study among all female patients who presented with acute kidney injury post pregnancy between October 2002 to April 2016 in department of nephrology in a tertiary care hospital in northern India and diagnosed as pregnancy induced TMA. The patient were assessed for duration of onset of renal failure to time of diagnosis of TMA, role of modality of treatment ie plasmpaharesis to outcome. These patients were assessed for complete, partial or no recovery in renal functions at 60 days after admission. RESULTS: Patients whose time of onset of renal failure to a correct diagnosis of TMA was ≤15 days and age less than 30 years was also associated with good prognosis. The patients who received plasma exchange and that to within 72 h of admission had more chances of recovery. CONCLUSIONS: Early diagnosis of disease and early institution of plasma exchange therapy improves renal outcomes in postpartum TMA.