Immunoglobulin A Nephropathy Presenting in Young Adults as Advanced Chronic Kidney Disease and Posttransplant Early Recurrence: A Case Series.

Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease, leading to chronic kidney disease. The disease is characterized by microscopic hematuria, gross episodic hematuria, hypertension, and subnephrotic proteinuria with or without renal function impairment. It affects individuals of all age groups, commonly seen in 10-40 years of age. It is progressive in nature and leads to chronic kidney disease, necessitating renal replacement therapy. This case series of in a tertiary care hospital in Western India highlights the presentation of this disease in young adults, its aggressive course, its rapid progression, and its early recurrence in the posttransplant period. It also summarizes the treatment recommendations for IgA recurrence in kidney recipients. The disease is known to have a high chance of posttransplant recurrence. Optimizing renin-angiotensin-aldosterone system (RAAS) blockade, blood pressure control, and increasing immunosuppression in rapidly deteriorating cases are the strategies recommended to treat IgA recurrence in kidney transplant recipients.

Correction to: Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.

Following publication of the original article [1], the authors reported errors in the presentation of Tables 2, 4 and 5.

Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.

BACKGROUND: Darbepoetin alfa (DA-α) is a long-acting erythropoiesis-stimulating glycoprotein which has half-life three-fold longer than that of Erythropoietin alfa (EPO). The objective of this study was to compare the efficacy and safety of DA-α injection versus EPO for treating renal anemia amongst Indian patients with end-stage renal disease (ESRD) undergoing dialysis. METHODS: Patients of either gender (aged 18-65 years) with ESRD undergoing dialysis who had hemoglobin (Hb) levels < 10 g/dL after receiving EPO were switched to DA-α (0.45 µg/kg) once weekly subcutaneously or EPO 50 IU/kg thrice weekly subcutaneously (centrally randomized 1:1) for 12-24 weeks (correction phase) followed by 12 weeks maintenance phase (for Hb levels ≥10 g/dL). The primary efficacy endpoint was mean change in Hb level from baseline to end of correction phase. RESULTS: In the intention-to-treat population (n = 126), the between group difference in mean Hb change was - 0.01 g/dL (95% CI - 0.68 to - 0.66, p = 0.97). After adjusting for covariates, the difference was - 0.2878 g/dL (95% CI -0.936 to0.360). The lower limit of the two-sided 95% CI of primary endpoint was above the pre-specified non-inferiority margin of - 1.0 g/dL. Similar trend of non-inferiority was observed for per-protocol population. Safety profile of DA-α and EPO were observed to be similar. CONCLUSION: Our study results demonstrated that for patients with ESRD undergoing dialysis, administering DA-α at lower dose frequency, is equally effective and well tolerated as EPO for treating renal anemia. TRIAL REGISTRATION: CTRI/2012/07/002835 [Registered on: 27/07/2012]; Trial Registered Prospectively.

A Prospective Study of Acute Kidney Injury According to KDIGO Definition and its Mortality Predictors.

BACKGROUND: Acute kidney injury is no longer considered to be an innocent bystander merely reflecting co-existent pathologies but an independent risk factor for mortality in the ICU. AIMS AND OBJECTIVES: To study clinical profile and correlation of patients with acute kidney injury (AKI) according to KDIGO definition with respect to incidence, outcome and different causes of AKI in critical care unit. STUDY DESIGN AND SETTING: It is a prospective observational study; and was carried out in the ICU of a tertiary care, teaching, public hospital. MATERIAL AND METHODS: We studied 316 patients developing AKI in ICU over a period of 1 year. RESULTS AND CONCLUSION: Incidence of AKI in our ICU was 37.71% and mortality rate was 51.9%. Tropical Acute febrile illnesses followed by sepsis were the most common causes of AKI in ICU. Most common cause of AKI among tropical acute febrile illnesses (AFI) was malaria and among sepsis group was lung infection. In our study KDIGO staging could not predict outcome because majority of patients had multisystem failure. Pre-existing co-morbidities, multi-organ system failure were associated with high mortality. APACHE II scoring system under- predicted the mortality in patients with AKI.

Safety and Efficacy of Acute Central Venous Catheters for Hemodialysis with Sodium Bicarbonate versus an Antibiotic Catheter Locking Solution.

This study was conducted to determine the safety and efficacy of acute central venous catheters (CVC) using a sodium bicarbonate catheter locking solution (SBCLS) versus an antibiotic catheter locking solution (ACLS). Our study included patients aged >18 years on hemodialysis initiated through an internal jugular non-tunneled CVC. Safety was assessed by comparing catheter loss resulting from catheter dysfunction (CD) and catheter-related blood stream infections (CRBSI) in two study groups: the SBCLS group (using 7.5% sodium bicarbonate) and the ACLS group (using antibiotic + heparin). Efficacy was assessed by the adequacy of blood flow (>300 mL/min). In total, 160 patients were included: 80 with the SBCLS and 80 with the ACLS. There were no statistically significant differences in clinical demographics between the groups. The average duration of the catheters was 23 days in the ACLS group and 22 days in the SBCLS group. In the ACLS group, four lost catheters to CD, two lost them to CRBSI, and five lost them to other malfunctions. Adequate blood flow was achieved in 71 patients. In the SBCLS group, three lost catheters to CD, three lost them to CRBSI, and four lost them to other malfunctions. Adequate blood flow was achieved in 73 patients. No significant differences between the groups were observed for catheter loss to CRBSI (P = 0.648), CD (P = 0.699), malfunction (P = 0.731), and blood flow (P = 0.598). The safety and efficacy of non-tunneled CVC with sodium bicarbonate as the catheter locking solution were similar to those of the ACLS.

Acute Kidney Injury in COVID-19: Clinical Profile and Outcome.

Introduction: Acute kidney injury (AKI) can be a severe complication of the coronavirus 2019 (COVID-19) infection. Follow-up data of these AKI patients, including the rate of progression to chronic kidney disease (CKD), is limited. Methods: COVID-19 patients with AKI, admitted from June 1, 2020, to August 25, 2020, were enrolled prospectively. Their clinical profile, biochemical investigations, urine analysis, treatment, and outcome in terms of mortality or discharge were analyzed. The discharged patients were followed up 3 months later to determine their renal recovery status. Results: AKI was noted in 146 out of 4,613 COVID-19 patients with an incidence of 3.16%. The outcome was available for 111 patients. According to the KDIGO (Kidney Disease Improving Global Outcomes) AKI criteria, 20 (18%) patients were in Stage 1, 16 (14%) in Stage 2, and 75 (68%) in Stage 3 AKI. Proteinuria and hematuria were present in 66% and 41%, respectively. Renal replacement therapy (RRT) was required in 45 (40.5%) patients. A total of 53 (47.7%) patients turned RT-PCR negative and were discharged. The renal recovery at discharge was complete in 31 of 111 (28%), partial in 20 of 111 (18%), and none in two (2%) patients. At 3 months follow-up of discharged patients, total mortality rate was 55.85%. Twenty three of 53 (43%) recovered their renal functions to baseline and 26 of 53 (49%) had progressed to CKD. Diabetes mellitus, dyspnea, altered sensorium, severe acute respiratory distress syndrome, need for RRT, lymphopenia, high neutrophil-lymphocyte ratio, hyperglycemia, raised inflammatory markers, and hematuria were associated with high mortality rate and reached statistical significance. Conclusion: AKI in COVID-19 patients has a high mortality rate (55.85%) with a high CKD progression rate among survivors (49%).

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.

Clinical Profile and Outcome of Hemodialysis Patients with SARS COV2 Infection in a Tertiary Care Centre in Mumbai, India.

INTRODUCTION: CKD5D is a high risk subgroup with high comorbidity burden, need for frequent visits to dialysis centre and a compromised immune system. The effect of SARS COV2 virus on this population is not well known. METHODS: This prospective study enrolled, all CKD5D with COVID 19 infection, admitted to our hospital, from 23rd April to 30th June 2020 & whose outcome as discharge/mortality was known. Their clinical profile, investigations, treatment and outcome in terms of mortality or discharge after clearing infection was noted and analysed. RESULTS: Total 203 dialysis patients with COVID 19 were referred to our institute. Of these total, 131 were analysed. Median age was 50 years (19-80 years) with 57% were males. Hypertension (76%) was the commonest comorbidity followed by diabetes (29%) and coronary artery disease (22%). Dyspnoea, fever and cough were present in 50%, 40%, and 33% patients respectively. 26% were asymptomatic. None had dialyser clotting. Mortality was 20.6%. Time to turn RT PCR negative was 14 days (3-40 days). Comparing deceased vs survivors: Age [56 vs 49 yrs], diabetes [56% vs 22%], duration of symptoms at admission [5 vs 4 days], dyspnea [85% vs 40%] and encephalopathy [30% vs 1%] at admission, bilateral opacities on Chest X ray [93% vs 20%] and high leucocyte count [11,059 ± 5,929 vs 7,022 ± 2,935/cmm] were statistically significant variables associated with mortality. CONCLUSION: Asymptomatic group was 26% of the total CKD5D with COVID 19 infection population analysed. Mortality was 20.61%. Higher age, later presentation to hospital, diabetes, dyspnoea, & encephalopathy at presentation, bilateral opacities on Chest X- Ray & higher leukocyte counts were significantly associated with mortality.

Renal and Hepatic Outcomes after Remdesivir Therapy in Coronavirus Disease-2019-Positive Patients with Renal Dysfunction at Baseline or after Starting Therapy.

We aimed to study the effect of remdesivir therapy on renal and hepatic function in coronavirus disease-2019 (COVID-19) patients with renal dysfunction at baseline or after starting therapy and identify the factors, if any, related to the efficacy of remdesivir therapy on patient outcome. Patients included in the study were those who met all the following criteria irrespective of baseline glomerular filtration rate [including those already on maintenance hemodialysis (HD)] or baseline deranged liver function test. (1) Age >18 years, (2) COVID-19 reverse transcriptase-polymerase chain reaction positive, (3) Meeting criteria for administration of remdesivir - [any one of the following: (a) COVID-19 pneumonia with respiratory rate >30/min or SPO2<94% on room air, (b) Acute respiratory distress syndrome (ARDS)]. (4) Renal dysfunction at baseline, during or within 48 h of completion of therapy. Thirty-four patients had renal dysfunction at baseline or developed it after remdesivir therapy - 16 were acute kidney injury (AKI), 10 chronic kidney diseases (CKD), four CKD stage 5D, and four were postrenal transplant. The overall mortality was 18/34 (52.9%). Eight out of 30 (26.66%) needed HD during or after therapy and of these, 15 died and among 15 survivors, 14 returned to their baseline renal function after cessation of therapy, one patient is still dialysis dependent. In the dialysis-dependent CKD (n = 4) subgroup, three died and one was discharged. In the postrenal transplant (n = 4) group, all developed AKI during or after the completion of therapy. None required HD, two returned to their baseline renal function, and two died. Only five had alanine aminotransferase elevation (×1 upper limit of normal) during or within 48 h of completion of therapy - three died and two returned to baseline. Lower PaO2/FiO2 (severe ARDS) (P = 0.0001), higher C-reactive protein (P = 0.022), higher serum lactate dehydrogenase (P = 0.038), and duration of symptoms before starting therapy (P = 0.05) were statistically significant variables at baseline associated with higher mortality. Remdesivir can be tried in moderate-to-severe COVID-19 cases with renal dysfunction as a complete recovery of renal function was noted in survivors. However, larger and well-controlled studies evaluating its safety and efficacy in patients with AKI and CKD are needed.

Pulmonary Hypertension in Various Stages of Chronic Kidney Disease in Indian Patients.

The prevalence of pulmonary hypertension (PH) in chronic kidney disease (CKD) in Indian patients has been evaluated in this study. In addition, association of PH with CKD etiology, its prevalence in various CKD stages, correlation between the severity of PH with CKD duration, various related biochemical parameters, and their relation to PH in CKD patients were analyzed. This cross-sectional and prospective study included 200 CKD patients. Detailed history and clinical examination were recorded. Hemoglobin, blood urea nitrogen (BUN), serum creatinine, albumin, and calcium-phosphorus product were recorded. Pulmonary function test was evaluated and two-dimensional echo was done 4 hours post dialysis. The prevalence of PH in CKD patients was 60.5%, with mean pulmonary artery systolic pressure (PASP) of 38.52 ± 7.32 mmHg. The mean age of those with PH was 47.85 ± 13.09 years. PH was more common in males (p = 0.03). The prevalence of PH increased as CKD stage advanced (p < 0.001). Diabetes and hypertension had a strong association with PH (p < 0.001). The prevalence (p = 0.003) and severity (p = 0.011) of PH increased with increase in CKD duration. In patients on hemodialysis (HD), the prevalence (p < 0.001) and severity (p = 0.022) of PH was significant compared to those on conservative treatment. The prevalence (p < 0.001) and severity (p < 0.001) of PH significantly increased as duration of HD increased. The prevalence of PH was significantly higher in patients with arteriovenous fistula (p = 0.002). Serum creatinine (p = 0.02) and serum calcium-phosphorus product (p < 0.001) were significantly higher in patients with PH. The prevalence of PH in CKD patients was 60.5%. There was a positive correlation between PH and duration of CKD, duration of HD, BUN, serum creatinine, and serum calcium-phosphorus product.

Long-term evaluation of kidney function in live-related kidney donors.

The consequences of live kidney donation on the donor health with main emphasis on postdonation blood pressure (BP), proteinuria, kidney size, and glomerular filtration rate (GFR) were evaluated. Twenty-five donors with minimum of six months postdonation duration were included in the study. Donor age at nephrectomy, duration postnephrectomy, systolic and diastolic BP measurement pre-and post-donation, postdonation, blood urea nitrogen, serum creatinine and 24-h proteinuria, blood sugar, two-dimensional echocardiogram were recorded. Kidney sizes pre-and post-donation were noted. GFR was calculated by chronic kidney disease epidemiology collaboration and modification of diet in renal disease formula and measured by diethylene triamine pentaacetic acid renogram in all donors pre-and post-donation. Twenty-one (84%) were female, and four (16%) were male. The mean age at donation was 46.24 ± 9.62 (28-65) years. Median duration postdonor nephrectomy was 26 (minimum 7 and maximum 228) months. There was a mean rise of 6.24 mm Hg in systolic and 4.20 mm Hg diastolic BP (P = 0.001). Remnant kidney size increased from 35.12 ± 6.80 to 42.32 ± 8.59 sq cm (P <0.0001). There was reduction of postdonation GFR from 94.50 ± 18.12 mL/min to 60.48 ± 14.32 mL/min after nephrectomy (P <0.0001). There was significant increase in remnant kidney GFR from 48.83 ± 7.79 mL/min to 60.48 ± 14.32 mL/min (P <0.0001). Two donors had hypertension postdonation while 23 did not. No donor developed postdonation proteinuria. A significant increase in the kidney size and GFR was evident in remnant native kidney in all. No mortality was observed.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC by intranasal administration of multiple escalating dose in healthy male subjects.

A novel corticosteroid compound (short form of IUPAC name: SFDAC) has been discovered by Sun Pharma Advanced Research Company (SPARC) Ltd. A randomized, observer-blind, active-controlled, parallel-groups, intranasal multiple escalating dose study was conducted in healthy male subjects to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC formulated as an aqueous suspension for intranasal administration. Intranasal sprays of SFDAC, active control fluticasone propionate (FP) and placebo were administered once in a day for 14 days as per randomization. Various clinical evaluations including 24-hour serum cortisol and urinary free cortisol (UFC) profiles were carried out. Blood samples were collected at pre-defined time-points and analyzed using a validated chromatographic method for estimation of SFDAC and its metabolite. The results of the study indicate that multiple dose of SFDAC intranasal spray upto 3,200 µg is safe and tolerated. Clinically significant suppression of hypothalamic pituitary adrenal (HPA) axis was not observed. The plasma concentration of SFDAC was found to be below the lower limit of quantification (LLQ) at most time-points for all subjects. SFDAC M1 metabolite was detected only at picogram level in plasma. The safety and pharmacokinetic characteristics of SFDAC observed in this study support further clinical development of the SFDAC nasal spray.

Audiometric profile in patients with chronic renal failure.

OBJECTIVES: To determine the occurrence of hearing loss and to establish audiometric profiles and patterns of hearing impairment in patients with chronic renal failure (CRF). METHODS: A retrospective study examined the relationship between the different stages of CRF and corresponding audiologic findings in those patients. Twenty-three subjects (46 ears) in the age range of 25 to 60 years were included in the study. These subjects were arranged into groups ranging from the second to fifth stages of CRF. Audiologic assessment in each subject was performed using a battery of tests, which included pure-tone audiometry, transient otoacoustic emission (TOAE), distortion product otoacoustic emission, and brainstem evoked response audiometry (BERA). RESULTS: Significant differences in the degree of hearing loss were observed among patients with different stages of CRF. It was noted that almost all (95.65%) patients with CRF did not pass the TOAEs. It was important to notice that none of the patients with CRF showed findings on BERA that pointed to retrocochlear involvement. Thus, the present study found that most patients (65.21%) had a cochlear pathology. CONCLUSIONS: We observed that (a) there is a high incidence of hearing loss among patients with CRF; (b) the methods of treatment (hemodialysis and conservative treatment) may not influence the impact of the disease on hearing; (c) levels of serum electrolytes and biochemical constituents of blood do not seem to correctly reflect the audiologic status of a CRF patient; and (d) hearing loss in patients with CRF has a distinct audiologic pattern. Given that CRF involves hearing loss, routine audiologic assessment in patients with this condition is essential.