A Unified Citywide Dashboard for Allocation and Scheduling Dialysis for COVID-19 Patients on Maintenance Hemodialysis.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused significant global disruption, especially for chronic care like hemodialysis treatments. Approximately 10,000 end-stage kidney disease (ESKD) patients are receiving maintenance hemodialysis (MHD) at 174 dialysis centers in Greater Mumbai. Because of the fear of transmission of infection and inability to isolate patients in dialysis centers, chronic hemodialysis care was disrupted for COVID-19-infected patients. Hence, we embarked on a citywide initiative to ensure uninterrupted dialysis for these patients. Materials and Methods: The Municipal Corporation of Greater Mumbai (MCGM) designated 23 hemodialysis facilities as COVID-positive centers, two as COVID-suspect centers, and the rest continued as COVID-negative centers to avoid transmission of infection and continuation of chronic hemodialysis treatment. Nephrologists and engineers of the city developed a web-based-portal so that information about the availability of dialysis slots for COVID-infected patients was easily available in real time to all those providing care to chronic hemodialysis patients. Results: The portal became operational on May 20, 2020, and as of December 31, 2020, has enrolled 1,418 COVID-positive ESKD patients. This initiative has helped 97% of enrolled COVID-infected ESKD patients to secure a dialysis slot within 48 hours. The portal also tracked outcomes and as of December 31, 2020, 370 (27%) patients died, 960 patients recovered, and 88 patients still had an active infection. Conclusions: The portal aided the timely and smooth transfer of COVID-19-positive ESKD patients to designated facilities, thus averting mortality arising from delayed or denied dialysis. Additionally, the portal also documented the natural history of the COVID-19 pandemic in the city and provided information on the overall incidence and outcomes. This aided the city administration in the projected resource needs to handle the pandemic.

Adipokine interactions promote the pathogenesis of systemic lupus erythematosus.

BACKGROUND: Adipokines are chemical mediators released from adipose tissue involved in regulation of appetite, insulin sensitivity, immune system and inflammatory responses. Adipokines contributes to low grade inflammatory response in autoimmune disease like Systemic Lupus Erythematosus (SLE) but the pathophysiology is yet not clear. The aim of this study is to understand role of adipokine interactions in SLE disease pathogenesis. METHODS: Sixty newly diagnosed treatment naïve SLE patients fulfilling the ACR criteria and forty age-sex matched healthy subjects were enrolled in thiscase-control study. Disease activity in SLE patients was evaluated using SELENA-SLEDAI. Array of adipokines, C1q circulating immune complexes (C1q-CIC), anti-C1q, anti-ribososmal P0 (anti-RibP0) and anti-mitochondrial antibodies (AMA) levels were detected by ELISA. Antinuclear antibodies (ANA) and anti-dsDNA autoantibodieswere detected by Indirect Immunofluorescence (IIF), while antigen specificities were detected by Immunoassay blot. Serum levels of C3 and C4 complement factors were assessed by nephlometer. RESULTS: Statistically significant elevation in progranulin, adipsin and resistin levels was seen among SLE patients when compared to healthy controls (p < 0.0001). Leptin and omentin levels were significantly reduced in SLE patients (p < 0.0001). There was no statistically significant difference in serum adiponectin, chemerin and visfatin levels when these two groups were compared (p > 0.05). Adiponectin, adipsin and resistin levels were elevated in SLE patients with renal manifestations (p < 0.05). Reduced leptin levels were significantly associated with presence of renal manifestations (p < 0.05). Adiponectin levels positively correlated with disease activity (r = 0.294, p = 0.027) whereas negatively correlated with C3 levels (r = -0.439, p = 0.0007). A positive correlation was observed between hypocomplementemia and leptin levels (p < 0.05). Leptin levels were negatively correlated with disease activity, anti-dsDNA, C1q-CIC and anti-C1q levels (p < 0.05). A significant positive correlation was observed between progranulin levels and anti-ribosomal P0 antibodies (r = 0.499, p < 0.0001). CONCLUSION: Adipokines levels and associated clinical manifestations suggest involvement of adipokines in disease pathogenesis of SLE. SLE disease activity and complement components may suggest regulatory effect of adipokines (adiponectin and leptin) on disease pathogenesis. Further studies on adipokines in SLE patients with renal manifestations may propose them as prognostic markers in renal damage. TRIAL REGISTRATION: NA.

Predictors of coronary calcification in Indian hemodialysis patients.

Several biomolecules potentially serve as promoters or inhibitors of calcification in dialysis patients which include fetuin A, matrix gla protein, osteopontin, osteoprotegerin, etc. The primary aim was to compare the biomarkers of coronary artery calcification (CAC) and to study its role as predictors of CAC in hemodialysis (HD) patients. Of 126 patients undergoing chronic HD, 100 patients completed the study. Blood samples were drawn for serum creatinine, electrolytes, calcium, phosphorus, Vitamin D3, parathyroid hormone (PTH), lipid profile, high sensitivity C-reactive protein, ferritin, fetuin A, and fibroblast growth factor-23 (FGF-23). Non-contrast Computed Tomography scan of the coronary arteries was conducted on all participants. Participants who were positive for CAC (P group) were compared with those negative for CAC (N group) using two sample t-test. Multiple logistic regression analysis was conducted to determine the predictors of CAC. The prevalence of vascular calcification (VC) was 60% with higher prevalence seen in males (71%), older age group, patients with dialysis vintage >5 years (27%), and diabetic population (62%). Mean serum phosphorus was significantly higher (P <0.001) and fetuin A (P <0.001) was significantly lower in the P group. Age (OR: 1.2, P = 0.004), serum phosphorus (OR: 1.8, P = 0.024), and fetuin A (OR: 0.0006, P = 0.001) were found as predictors of CAC. CAC was more prevalent in males, patients with higher age group and in those with longer dialysis vintage and diabetic population. Participants with CAC exhibited significantly high phosphorus and low fetuin A levels. Age, phosphorus level, and fetuin A were found to be predictors of CAC in dialysis patients. FGF-23 could not predict CAC.

Subcutaneous Phaeohyphomycosis Caused By Pyrenochaeta Romeroi in a Kidney Transplant Recipient: A Case Report.

Infections are Achilles heel of kidney transplant recipients. Opportunistic fungal infections are increasingly recognized in these patients. We report a case of kidney transplant recipient with skin and soft tissue infection caused by Pyrenochaeta romeroi, a dematiaceous fungi. Infection by this organism is rare.

Epidemic of Chemical Peritonitis in Patients on Continuous Ambulatory Peritoneal Dialysis: A Report from Western India.

While non-infectious etiologies like chemical irritants are rare causes of epidemics of peritonitis, this possibility should be considered when one encounters an unusual clustering of peritonitis cases. We describe here an epidemic of chemical peritonitis at our center.

A cross-sectional study of dialysis practice-patterns in patients with chronic kidney disease on maintenance hemodialysis.

We studied the dialysis practice-patterns with regard to various aspects of chronic kidney disease (CKD) stage 5D, like anemia, mineral bone disease, vaccination, hospitalization, hypertension and cost of therapy. Four hundred and sixty-four adult hemodialysis (HD) patients from various dialysis centers of Mumbai were included in the study. The mean age of the study patients was 47.2 years. Temporary dialysis catheters were the most common initial vascular access. Thirteen percent of prevalent HD patients were on temporary catheters; 33% of patients had history of failure of arterio-venous fistula. The most common cause of failure was access thrombosis. About 75% of the patients had hemoglobin <11 g/dL and 35% had uncontrolled blood pressure. The prevalence of positive hepatitis B surface antigen and anti-hepatitis C virus antibody was 6% and 2%, respectively. The average cost of HD treatment was approximately 6100 Indian rupees (about US $100). HD is helpful in treating many of the clinical manifestations of CKD and postpones otherwise imminent death. However, dialysis treatment is no panacea to renal failure; HD patients have higher hospitalization rates and lower quality of life than the general population. The therapy itself brings with it a unique set of problems, such as vascular access-related complications, which cause significant mortality and morbidity. This study was a study of the current HD practices. The primary goal of this cross-sectional observational study is to understand dialysis practices and obtain data that can be used to improve care in the future.

Seropositivity for Antibodies to DRS-G, a Virulence Factor from Streptococcus dysgalactiae subsp. equisimilis, Is an Independent Risk Factor for Poststreptococcus Glomerulonephritis and Chronic Kidney Disease in Mumbai, India.

The disease spectrum caused by Streptococcus dysgalactiae subsp. equisimilis resembles that of S. pyogenes (group A streptococcus [GAS]). These two bacterial species are closely related and possess many common virulence characteristics. While some GAS strains express virulence factors called streptococcal inhibitor of complement (SIC) and distantly related to SIC (DRS), some S. dysgalactiae subsp. equisimilis isolates express an orthologue of DRS, which is referred to as DRS-G. We reported previously that seropositivity for either anti-SIC or anti-DRS antibodies (Abs) is associated with poststreptococcal glomerulonephritis (PSGN). However, only seropositivity for anti-SIC Abs is associated with chronic kidney disease (CKD). We now extend the study to test whether seropositivity for anti-DRS-G Abs is also associated with these renal diseases. Stored serum samples collected for our previous study were tested by an enzyme-linked immunosorbent assay (ELISA) for Abs to DRS-G. The samples represented sera from 100 CKD adult patients, 70 adult end-stage renal disease (ESRD) patients, 25 PSGN pediatric patients, and corresponding age-matched control subjects. The proportion of PSGN, CKD, and ESRD patients who showed seroreaction to anti-DRS-G Abs was significantly higher than that of the corresponding age-matched controls, who in general exhibited seropositivity rates commensurate with the isolation rate of drsG-positive S. dysgalactiae subsp. equisimilis in the community during this study period. Since higher rates of seropositivity for anti-DRS-G Abs in the renal disease categories are resultant of previous infections with DRS-G-positive S. dysgalactiae subsp. equisimilis strains, we conclude the seropositivity is an additional risk factor for these renal diseases. In this regard, anti-DRS-G Abs have attributes similar to those of the anti-SIC Abs.

Antibodies to group A streptococcal virulence factors, SIC and DRS, increase predilection to GAS pyoderma.

BACKGROUND: Streptococcus pyogenes (group A streptococcus; GAS) is an etiological agent for pharyngitis, pyoderma, and invasive infections in humans. Pharyngitis and pyoderma may lead to serious immune sequelae such as rheumatic heart disease and post-streptococcal glomerulonephritis (PSGN). Streptococcal Inhibitor of Complement (SIC) and its orthologue, distantly related to SIC (DRS), are virulence factors expressed by only four of more than 100 M types of GAS. These four types (M1, M57, M12 and M55) are among the M types, which are associated with PSGN. In several populations PSGN has been shown to be a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Previous studies showed SIC or DRS antibody-prevalence was associated with PSGN, and seroprevalence of SIC antibodies is significantly high among CKD and ESRD patients in Mumbai. METHODS: Streptococcal isolates recovered from GAS pyoderma cases were typed. Seropositivity for SIC and DRS antibodies in subjects with pyoderma, PSGN pediatric cases, age matched healthy controls and non-GAS pyoderma cases were determined. RESULTS: We confirm in this study an association between seroprevalence to SIC and DRS antibodies, and PSGN in Mumbai population despite low point prevalence of M1, M12, M55 and M57. In addition we extended the study to GAS-pyoderma and non-GAS pyoderma cases. To our surprise, we found a positive association between the seroprevalence to SIC and DRS antibodies, and GAS-pyoderma owing to infection with diverse M types. The mechanism of increased predisposition to pyoderma owing to infection by diverse GAS among SIC or DRS antibody-positive population is not clear. Nonetheless, our findings could be explained by a phenomenon akin to antibody-dependent enhancement (ADE). CONCLUSIONS: This is the first report showing a small number of GAS M types conferring predisposition to pyoderma by diverse types. Implications of this ADE-like phenomenon are discussed in the light of evolutionary advantage to GAS, vaccine design and control of renal diseases.

Late-Onset Cytomegalovirus Gastritis in Low-Risk Renal Allograft Recipients.

OBJECTIVES: Skin grafting has been evolving as an important application in reconstructive surgery. Mixed reports about the survival of allogeneic and xenogeneic keratinocytes require further substantiation to determine the role of these cells in wound healing. MATERIALS AND METHODS: Rabbit and rat skins were recovered and cultured in vitro. Full-thickness wounds were created on the dorsum of rabbits (2 cm × 2 cm; n = 4). Cultured epithelial autograft, allograft, and xenograft cells were sprayed onto 3 freshly created wounds, with 1 wound acting as a control. The wounds were monitored every 2 days for 4 weeks. After 4 weeks, the rabbits were killed; skin biopsies were taken from each healed wound and stained with hematoxylin and eosin, and epidermal thickness was measured. RESULTS: All examined grafts showed favorable healing outcomes because the wounds appeared similar to normal skin upon healing. The only observed significant difference was the thickness of the epidermis layer, which was thinner in the xenograft (P = .002) than the autograft or allograft. Morphologic evaluation of the skin surface showed that the rat skin was thinner than the rabbit skin. The graft that achieved the best result was the autograft because the thickness was similar to and mimicked normal skin. CONCLUSIONS: All 3 grafts (autograft, allograft, and xenograft) have the potential to reconstitute epithelial defects. This approach can overcome the limitation of autologous skin donor sites, especially in burn cases.

Earlier-start versus usual-start dialysis in patients with community-acquired acute kidney injury: a randomized controlled trial.

BACKGROUND: Optimum timing of the initiation of dialysis therapy in acute kidney injury is not clear. STUDY DESIGN: Prospective, open label, 2-arm, randomized, controlled trial. SETTING & PARTICIPANTS: 208 adults with acute kidney injury with progressively worsening azotemia at the artificial kidney dialysis unit of a tertiary-care referral center in western India. INTERVENTION: Earlier-start dialysis was initiated when serum urea nitrogen and/or creatinine levels increased to 70 and 7 mg/dL, respectively, whereas the usual-start dialysis patients (control group) received dialysis when clinically indicated as judged by treating nephrologists. OUTCOMES: Primary outcome was in-hospital mortality and dialysis dependence at 3 months. Secondary outcome in patients receiving dialysis was time to recovery of kidney function, computed from time of enrollment to the last dialysis session. RESULTS: Of 585 screened patients, 102 were assigned to earlier-start dialysis, and 106 to usual-start dialysis. Baseline characteristics were similar between randomized groups. 93 (91.1%) and 88 (83.1%) participants received dialysis in the intervention and control groups, respectively. Mean serum urea nitrogen and serum creatinine levels at dialysis therapy initiation were 71.7 ± 21.7 (SD) and 7.4 ± 5.3 mg/dL, respectively, in the intervention group versus 100.9 ± 32.6 and 10.41 ± 3.3 mg/dL in the control group. Data on primary outcome were available for all patients. In-hospital mortality was 20.5% and 12.2% in the intervention and control groups, respectively (relative risk, 1.67; 95% CI, 0.88-3.17; P = 0.2). 4.9% and 4.7% of patients in the intervention and control groups, respectively, were dialysis dependent at 3 months (relative risk, 1.04; 95% CI, 0.29-3.7; P = 0.9). LIMITATIONS: Study was not double blind, event rate (ie, mortality) was less than predicted, wide CIs preclude definitive findings. CONCLUSIONS: Our data do not support the earlier initiation of dialysis therapy in community-acquired acute kidney injury.

Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease.

BACKGROUND: Group A streptococcus (GAS) is an etiological agent for the immune mediated sequela post streptococcal glomerulonephritis (PSGN). In some populations PSGN is recognized as a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). It was found that a significantly greater proportion of subjects with past history of PSGN than without the history exhibited seroreactions to streptococcal antigens called streptococcal inhibitor of complement (SIC) and to distantly related SIC (DRS). These antigens are expressed by major PSGN-associated GAS types. We therefore predicted that in populations such as India, which is endemic for streptococcal diseases and which has high prevalence of CKD and ESRD, greater proportions of CKD and ESRD patients exhibit seroreaction to SIC and DRS than healthy controls. METHODS: To test this we conducted a SIC and DRS seroprevalence study in subjects from Mumbai area. We recruited 100 CKD, 70 ESRD and 70 healthy individuals. RESULTS: Nineteen and 35.7% of CKD and ESRD subjects respectively were SIC antibody-positive, whereas only 7% of healthy cohort was seropositive to SIC. Furthermore, significantly greater proportion of the ESRD patients than the CKD patients is seropositive to SIC (p=0.02; odds ratio 2.37). No association was found between the renal diseases and DRS-antibody-positivity. CONCLUSIONS: Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients.

Minimal-change disease in adolescents and adults: epidemiology and therapeutic response.

BACKGROUND: Epidemiology of minimal-change disease (MCD) in adults differs from that in children and is not studied well in Indian population. METHODS: We retrospectively studied the records of 61 adult patients with MCD to assess clinical, laboratory and histopathological features, and to evaluate the response to treatment, course and complications of the disease and therapy. RESULTS: The male to female ratio was 1.17:1. Mean age was 30.46 years. Of the total, 6.55% had hypertension; 13.11% had microhaematuria. After initial treatment with steroids, 68.85% had complete remission (CR) and 13.1% had partial remission (PR). Twelve of 14 (85.71%) steroid-resistant cases had CR or PR after alternative immunosuppression with cyclophosphamide, or mycophenolate mofetil. Of all patients, 44.2% had at least one relapse; 8.19% were frequently relapsing and 26.22% were steroid dependent. After a mean follow-up of 149.9 weeks, 38 (61.29%) patients were in CR and 16 (26.22%) in PR with a mean proteinuria of 1.28 g/day, 3 being treated for relapse. Mean serum creatinine was 89.28 µmol/L (1.01 mg/dL). Fourteen (22.95%) had acute kidney injury (AKI). All but two recovered completely. CONCLUSIONS: This single-centre study with a medium-term follow-up shows that majority of patients respond to steroids or alternative immunosuppressants. AKI is common and may not be completely reversible in some cases.

Laparoscopic donor nephrectomy versus open donor nephrectomy: recipient's perspective.

Effects of laparoscopic donor nephrectomy (LDN) on graft function, especially early post-transplant, have been controversial. To assess and compare early and late graft function in kidneys procured by open and laparoscopic methods, a retrospective observational study was carried out on 37 recipients-donors who underwent LDN after introduction of this technique in February 2007 at our center, a tertiary care nephrology referral center. Demographic, immunological and intraoperative variables as well as immunosuppressive protocols and number of human leukocyte antigen (HLA) mismatches were noted. Early graft function was assessed by serum creatinine on Days two, five, seven, 14 and 28 and at the time of discharge. Serum creatinine values at three months and at one year post-transplant were considered as the surrogates of late graft function. Data obtained were compared with the data from 33 randomly selected kidney transplants performed after January 2000 by the same surgical team, in whom open donor nephrectomy was used. Pearson's chi square test, Student's t test and Mann-Whitney U test were used for statistical analysis. Early graft function (serum creatinine on Day five 2.15 mg/dL vs 1.49 mg/dL, P = 0.027) was poorer in the LDN group. Late graft function as assessed by serum creatinine at three months (1.45 mg/dL vs 1.31 mg/dL, P = 0.335) and one year (1.56 mg/dL vs 1.34 mg/dL, P = 0.275) was equivalent in the two groups. Episodes of early acute graft dysfunction due to acute tubular necrosis were significantly higher in the LDN group (37.8% vs 12.1%, Z score 2.457, P = 0.014). Warm ischemia time was significantly prolonged in the LDN group (255 s vs 132.5 s, P = 0.002). LDN is associated with slower recovery of graft function and higher incidence of early acute graft dysfunction due to acute tubular necrosis. Late graft function at one year is however comparable.