Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience.

BACKGROUND: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients. METHODS: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes. RESULTS: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection. CONCLUSIONS: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.

Fulminant ruptured septic aneurysm complicating the catheter related blood stream infection in a patient on maintenance hemodialysis: A case report.

Metastatic infections can complicate catheter-related blood stream infections (CRBSI) in dialysis dependent patients. However, an infected/septic aneurysm involving the aorta or its branches as a direct complication of CRBSI without an underlying infective endocarditis is not reported so far in the literature. We report a 43-year female, who presented with CRBSI 2 weeks following a tunneled dialysis catheter (TDC) insertion. Due to the lack of defervescence after 72 h of antibiotics given as per the culture sensitivity reports, the TDC was removed. Blood cultures grew Pseudomonas aeruginosa. After a catheter free interval of 4 days, a TDC was reinserted, an antibiotic course was completed, and she was discharged in stable condition. Five days later, she presented with acute abdominal pain and fever. A tender, firm, and pulsatile mass was noted in the hypogastrium with a bruit. Contrast-enhanced CT revealed a pseudoaneurysm of the aorta, and left common iliac artery at the site of origin. She was started on IV antibiotics and planned for an endovascular prosthesis but had a sudden collapse during her hospital stay due to a ruptured aneurysm. CRBSI due to certain pathogens such as Pseudomonas might require prolonged and dual antibiotic therapy to prevent fulminant complications.

Higher pro-inflammatory cytokines IL-6 and IFN-γ are associated with anti-SARS-CoV-2 spike protein-specific seroconversion in renal allograft recipients.

BACKGROUND: Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS-CoV-2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune-related complications. METHODS: RTRs, either acquired SARS-CoV-2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS-CoV-2, were recruited in the study. Thirty-five unvaccinated RTRs, without anti-SARS-CoV-2 spike protein-specific antibodies, were also included as control. Cytokines interleukine-6 (IL-6), interferon-γ (IFN-γ), TGF-ß, and IL-10 were measured using ELISA. The SARS-CoV-2 spike protein-specific IgG-titer was measured by chemiluminescent microparticle immunoassay methods. RESULTS: The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45-1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52-3838.75). The IL-6, IFN-γ, TGF-ß, and IL-10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro-inflammatory cytokines IL-6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN-γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non-seroconverter. Similarly, in the vaccination group, pro-inflammatory cytokines IL-6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN-γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non-seroconverter. In contrast, TGF-ß (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non-seroconverter. CONCLUSIONS: Pro-inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination in RTRs.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

Desmopressin Acetate Before Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with Renal Failure - Is it Really Beneficial?

Introduction: The most common complication of percutaneous renal biopsy is bleeding, which can be seen in up to one-third of cases. The aim of this study was to evaluate the effect of prebiopsy administration of intranasal desmopressin acetate in reducing the incidence of biopsy-related bleeding complications in patients with significant renal dysfunction who underwent renal biopsy. Methods: This was a retrospective, observational study of percutaneous native renal biopsies performed at our center from July 2014 to June 2018. Bleeding complication rates of patients with renal failure (estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2) who received desmopressin and those who did not receive desmopressin were compared. Results: Desmopressin administration before renal biopsy in patients with eGFR <30 mL/minute/1.73 m2 was associated with a significant reduction of bleeding complications (major and minor together; P = 0.025) and no significant reduction in major complications (P = 0.616) or intervention rates (P = 0.251) when compared with a group that did not receive desmopressin. Conclusions: While prebiopsy intranasal desmopressin use was associated with a significant reduction of overall bleeding complications including major and minor complications, there was no reduction in the rate of other major complications and interventions.

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.

Association of Human Leucocyte Antigen Polymorphism with Coronavirus Disease 19 in Renal Transplant Recipients.

Human leucocyte antigens (HLAs) are highly polymorphic glycoproteins expressed at the surface of all nucleated cells. It is required for the SARS-CoV-2 peptide antigen presentation to immune cells for their effector response. However, polymorphism in HLA significantly impacts the binding of SARS-CoV-2 antigenic peptide to the HLA pocket and regulates immune activation. In this study, 514 renal transplant recipients (RTRs) were recruited from the outpatient department and categorized either into symptomatic (n = 173) or asymptomatic groups (n = 341) based on Coronavirus disease-19 (COVID-19) symptoms. The anti-SARS-CoV-2 spike protein-specific IgG antibody titer was measured by chemiluminescent microparticle immune-assay methods in 310 RTRs. The HLA details of 514 patients were retrieved from the electronic medical records and analyzed retrospectively. We found that HLA antigen allele A*24 was significantly associated with asymptomatic infection in 22.78%, HLA C*02 in 4.51%, DRB1*12 in 10.85%, and HLA DQA1*02 in 27.74% of RTRs. Whereas HLA A*29 in 3.46%, A*33 in 26.01%, B*13 in 10.40%, DRB1*10 in 4.62%, DRB1*15 in 39.30%, DRB1*30 in 1.15%, and DQA1*60 in 3.57% of RTRs were associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease. The seroconversion rate in asymptomatic patients was 118/137 (86.13%), had a median titer of 647.80 au/ml, compared to symptomatic patients 148/173 (85.54%) with a median titer of 400.00 au/ml, which was not significant between the two groups (P = 0.88 and 0.13). In conclusion, HLA alleles A*24, C*02, DRB1*12, and DQA1*02 were significantly associated with asymptomatic infection, and A*29, A*33, B*13, DRB1*10, DRB*15, and DRB1*30 were significantly associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease.

High mortality and residual kidney damage with Coronavirus disease-19-associated acute kidney injury in northern India.

BACKGROUND: Acute kidney injury (AKI) is associated with morbidity and mortality in COVID-19 patients. The incidence of AKI and its outcomes vary in different parts of the world. We aimed to analyze the AKI incidence, predictors of AKI, mortality, and renal function outcomes on follow-up in hospitalized patients with COVID-19. MATERIALS AND METHODS: The study was designed as a retrospective, observational study of electronically captured data on the hospital information system of laboratory-confirmed COVID-19 patients, with and without AKI, between March 2020 to June 2021. The predictor of AKI and mortality and residual damage in recovered AKI patients were analyzed. RESULTS: Of the 3395 patients, 3010 COVID-19 patients were eligible. AKI occurred in 951 (31.5%); with stages 1, 2, and 3 in 605 (63.7%), 138 (14.5%), and 208 (21.8%) patients, respectively. AKI severity increased with COVID-19 severity. Of 951 AKI patients, 403 died, and 548 were discharged. AKI group had higher mortality (42.3%) than the non-AKI (6.6%). At discharge, complete recovery was noticed in 370(67.5%), while 178 (32.5%) had residual damage. At three months of follow-up, 108 (69.6%) of 155 patients showed complete recovery. Residual damage was observed in 47 (30.3%). In 14 (9%) patients, serum creatinine remained elevated above the baseline. Thirty-three (21.2%) patients showed proteinuria (n = 24) and microscopic hematuria (n = 9). CONCLUSIONS: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Residual kidney damage post-COVID-19 in recovered AKI patients may increase the CKD burden.

Renal graft malakoplakia masquerading post-transplant lymphoproliferative disorder.

A 45-year-old woman presented to us in March 2019 with complaints of fever and right lower quadrant abdominal pain for 1 month. She had undergone renal transplantation in 2017 for end-stage renal disease and developed four episodes of urinary tract infection in the next 16 months post transplantation, which were treated based on culture reports. She was subsequently kept on long-term prophylaxis with trimethoprim and sulfamethoxazole. Her present laboratory parameters showed a normal blood picture and elevated creatinine. Urine culture grew Escherichia coli Non-contrast CT of the abdomen-pelvis revealed an endo-exophytic hyperdense mass in the graft kidney showing local infiltration and associated few regional lymph nodes. PET-CT revealed the soft-tissue mass and regional lymph nodes to be hypermetabolic, raising the possibility of lymphoma. However, biopsy showed features of malakoplakia. She was subsequently initiated on long-term antibiotic therapy and her immunosuppression decreased.

Modalities of Diagnosis and Management of Peritoneal Dialysis-related Hydrothorax Including Videothoracoscopy-assisted Repair: A Single-center Experience.

Continuous ambulatory peritoneal dialysis (PD)-related hydrothorax (PDRH) is uncommon; however, it is associated with a high discontinuation rate and morbidity. We report clinical characteristics, pleural fluid chemistry patterns, diagnostic modality, management options, and outcomes in 12 patients who have confirmed pleuroperitoneal communication after the inception of the PD program at our institute. The incidence of PDRH in our study was 0.64%. The interval between initiation of PD and hydrothorax ranged from 7 weeks to 40 weeks (average 20.6 weeks). Ten (83.3%) had right-sided, one (8.3%) left-sided, and one (8.3%) bilateral hydrothorax. Most patients (83.3%) had dyspnea with chest symptoms, but two (16.6%) patients were asymptomatic. All patients had confirmed communication either by peritoneal scintigraphy or computed topography peritoneography. PD had to be stopped in two patients and patients were shifted back to hemodialysis. Pleurodesis, through thoracostomy with tetracycline or betadine, was used for four patients. Three patients underwent video-assisted thoracoscopy (VATS) with surgical repair of the diaphragmatic defect, and one underwent VATS assisted talc pleurodesis. All four patients who underwent VATS repair of the defect had successful outcomes. With availability and experience with VATS, most patients had successfully returned to PD with no recurrence and with minimal morbidity.

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.

Infection-Induced Kidney Diseases.

Infection induced kidney diseases are of concern for clinicians because timely detection and treatment of infections may cure or limit the extent of injury inflicted by microorganisms causing the infections. Infections can cause kidney injury by either direct invasion, or indirectly by immune mediated mechanisms, which manifest as post-infectious glomerulonephritis, or infection-related glomerulonephritis. Clinical manifestations may be acute or chronic depending on the microorganisms, endemic/epidemic nature and source of infection. All microbials virus, bacteria, mycobacteria, fungus, and protozoa have been implicated in kidney diseases either causing direct kidney injuries or immune-mediated injuries. Infection control practices in large parts of world is limited by poverty, social behavior, high population density, deforestation, inadequate access to safe drinking water, and poor health care facilities. Although, antimicrobials and vaccinations have successfully eradicated and cured many infectious diseases; however injudicious antimicrobial use and emergence of resistant organisms complicated the disease severity like secondary renal amyloidosis with chronic persistent infection. Re-emergence of various infections has been a recent pattern in developed world leading to uncertain diagnostic challenges, and association with kidney diseases.

Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes.

INTRODUCTION: Vascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) -1154 G/A, -2578 C/A, +936 C/T, and -2549 Ins/Del in chronic allograft nephropathy. METHODS: Blood samples were collected before renal transplantation, and DNA was extracted. Genotyping of VEGF SNPs -1154 G/A (rs1570360), -2578 C/A (rs699947), +936 C/T (rs112005313), and -2549 Ins/Del (18bpindel) polymorphisms were carried out. Relative quantification of VEGF-A mRNA expression for 4 VEGF SNPs were quantified by the 2-ΔΔCt algorithm. Kidney allografts were categorized into graft loss (n = 98) and normally functioning (n = 174) groups. Genotype frequencies were calculated using additive, dominant, and recessive models. Hardy-Weinberg Equilibrium was assessed between outcome groups by standard procedure using χ2 analysis. The cumulative allograft survival was estimated by Kaplan-Meier analysis and compared among VEGF genotypes by the log-rank test. Study limitations were the lack of VEGF serum levels, donor-specific antigens, and protocol biopsies. RESULTS: There was an association of AA (hazard ratio = 2.42, P = 0.0001) and CA (hazard ratio = 1.83, P = 0.009) genotypes of -2578 C/A SNP with graft loss. After adjustment for transplant-related covariates, associations of VEGF SNPs -2578 C/A and -2549 Ins/Del with graft failure were found to be significant. There was prolonged graft survival for cases with the CC genotype of VEGF -2578 C/A SNP. The carrier -2578*CC, -1154*GG, and +936*CC genotypes were shown to have a strongly protective association. There was no association with posttransplantation lymphomas. CONCLUSION: Recipients of kidney allografts possessing low-producing VEGF genotypes are associated with less prolonged graft survival.