Predictors of functional impairment and mortality in patients on maintenance hemodialysis.

INTRODUCTION: Numerous factors impact the mortality and functional abilities of patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis (MHD). We aimed to determine the mortality rate at 1 year of MHD, identify predictors of mortality, and assess functional impairments concerning activities of daily living (ADLs) and instrumental ADL (IADL). METHODS: Our study was prospective, observational cohort study that enrolled patients receiving MHD. We collected demographic, clinical, and laboratory data. We also assessed ADLs and IADLs for daily performance. RESULTS: Our study included 167 patients with a mean age of 51.6 ± 13.1 years, and 56.9% were male. Of these, 80 (47.9%) were diabetic, and 145 (86.8%) were hypertensive. The mortality rate after 1 year of MHD was 10.8%, and cardiovascular causes accounted for over 70% of total deaths. Sudden cardiac death was the most frequent cause (38.9%), followed by cardiogenic shock (22.2%). Older age and low parathormone levels (<300 pg/mL) were significantly associated with higher mortality rates. Mean ADL and IADL scores were 4.5 ± 1.3 and 6.3 ± 2.7, respectively. Eighteen (10.8%) and 56 (33.5%) patients had low ADL and IADL scores, respectively. Although statistically insignificant, a higher proportion of non-survivors exhibited low IADL and ADL scores. Older age, longer diabetes duration, and higher BMI levels were significantly associated with lower IADL scores. CONCLUSIONS: Older age and suppressed PTH levels are predictors of mortality in ESRD patients receiving MHD. These patients require regular follow-ups to rule out cardiovascular morbidity. Functional impairment is prevalent but remains underdiagnosed in MHD patients. It should be monitored regularly to improve quality of life in ESRD.

Deciphering mechanistic implications of antimicrobial and antioxidant potentials of certain new dibutyltin(IV) formulations as possible therapeutic options based on DFT and hybrid materials paradigm.

Mechanistic implications of antimicrobial and in vitro antioxidant potentials of a set of newly generated nonbridged mononuclear N,O-orthometallated and carboxylate bridged binuclear nonorthometallated dibutyltin(IV) formulations have been investigated. Some of these formulations were screened for their antibacterial and antifungal activities against Escherichia coli and Candida albicans, respectively whereas in vitro antioxidant potential was examined by Ferric reducing antioxidant power (FRAP) assay. Nonbridged mononuclear N,O-orthometallated dibutyltin(IV) formulations were generated by the reactions of Bu2 SnCl2 with sodium salts of 2-aminophenol/substituted 2-aminophenol and flexible N-protected amino acids in 1:1:1 molar ratio in refluxing dry THF. Plausible structures of these nonbridged mononuclear N,O-orthometallated dibutyltin(IV) formulations containing flexible N-protected amino acids have been suggested on the basis of spectroscopic and mass studies of some representative formulations. Plausible structures suggested on the basis of spectroscopic studies are corroborated by density functional theory (DFT/B3LYP method) (SPARTAN-20) investigation of a representative dibutyltin(IV) complex and the ligands involved in it. The presence of two different classes of organic ligands in this complex provides an opportunity to study optimized topologies, bonding, distortions, optimized energy, and stability of the complex.

First Successful Three-Way Kidney Exchange Transplantation in North India.

Kidney paired donation is the most cost-effective approach in incompatible donor-recipient pairs. Incompatibility may be due to blood group, human leucocyte antigen crossmatch or both. In many cases of a living donor kidney transplant, there is only one potential donor who becomes unsuitable due to any of the above mentioned factors. In kidney paired donation, donor-recipient pairs are exchanged to sort out the incompatibility. We report our first successful three-way kidney exchange transplantation from North India. As deceased donor program is still in evolving stage in most parts of our country and transplant with desensitization protocol is associated with financial constraints, infections, and lack of availability in many centers, kidney paired donation is a valuable approach to expand the donor pool.

INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Gender Bias in Kidney Donation in India: Has It Changed Over the Past 2 Decades?

OBJECTIVE: To study the trend among Indian women living kidney donation over the past 18 years and see if a gender bias still exists as described in literature before. METHODS: This is a retrospective, single-center, observational cohort study with data collected from the medical records department of all living donor kidney transplants between January 2001 to December 2018, which were categorized into 2 groups of 9 years each for comparison using categorical variables in form of number, percentage, χ2 test, and Pearson correlation coefficient. RESULTS: A total of 557 kidney transplants were analyzed, with women having 78.5% higher incidence of donation (P < .001). Among them, parents (72.20% mothers), spouses (87.20% wives), siblings (47.50% sisters), and children (44.44% daughters) were the major participants. Further analysis revealed wife donation reduced from 92.3% to 85.6% (P = .41) and mother donation reduced from 72.5% to 71.7% (P = .91), whereas sister donation increased from 28.5% to 51.5% (P = .14) and daughter donation increased from 0% to 44.4% during the 18-year period. Also, female to male donation decreased from 63.8% to 51.6% (P = .02) during the same period. Thus, the overall percentage of female donation is decreasing (73.9% to 61.4%, P = .01), and a significant negative correlation with time was observed in this study (correlation coefficient, r = -0.55, P = .017). CONCLUSIONS: A lot has changed over the past 18 years, with more male kidney donors now coming forward. Larger prospective studies are required to understand the diverse reason for this sex discrepancy.

A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney disease patients with anaemia.

BACKGROUND: Iron deficiency anaemia is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and is often treated with oral or intravenous (IV) iron therapy. This trial compared the efficacy and safety of IV iron isomaltoside 1000 (Monofer®) and oral iron in NDD-CKD patients with renal-related anaemia. METHODS: The trial was a Phase III open-label, comparative, multicentre, non-inferiority trial conducted in 351 iron-deficient NDD-CKD patients, randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sulphate administered as 100 mg elemental oral iron twice daily (200 mg daily) for 8 weeks (Group B). The patients in Group A were randomized into A1 (infusion of max. 1000 mg single doses over 15 min) and A2 (bolus injections of 500 mg over 2 min). A modified Ganzoni formula was used to calculate IV iron need. The primary end point was change in haemoglobin concentrations from baseline to Week 4. RESULTS: Iron isomaltoside 1000 was both non-inferior to oral iron at Week 4 (P < 0.001) and sustained a superior increase in haemoglobin from Week 3 until the end of the study at Week 8 (P = 0.009 at Week 3). The haemoglobin response was more pronounced with iron isomaltoside 1000 doses ≥1000 mg (P < 0.05). Serum-ferritin and transferrin saturation concentrations were also significantly increased with IV iron. Adverse drug reactions were observed in 10.5% in the iron isomaltoside 1000 group and 10.3% in the oral iron group. More patients treated with oral iron sulphate withdrew from the study due to adverse events (4.3 versus 0.9%, P = 0.2). CONCLUSIONS: Iron isomaltoside 1000 was more efficacious than oral iron for increase in haemoglobin and proved to be well tolerated at the tested dose levels in NDD-CKD patients.

Histopathological changes of radial artery wall in patients of chronic kidney disease stage 5 undergoing AV fistula formation and their correlation with serum iPTH levels.

Vascular complications arise in uremic patients in the absence of clinically significant atherosclerotic disease. Elevated serum parathyroid hormone (PTH) and abnormal calcium (Ca) and phosphorus (P) balance have been implicated in vascular damage in chronic kidney disease (CKD) patients, but there is lack of histo-pathological studies. Patients with CKD stage 5 and 5D who underwent arterio-venous fistula were included in this study. Baseline and laboratory parameters including assessment of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, albumin, calcium, phosphorus, intact PTH (iPTH) and vitamin D level were documented. The specimens of the arterial wall were obtained during the procedure and were analyzed. Patients were divided into two groups iPTH <400 (Group A) and iPTH >400 (Group B). Mean intimal thickness (IT) was significantly high in patients of Group B (60.4 ± 24.1 µ m) as compared with patients of Group A (37.8 ± 14.9 µm) (P = 0.003). Vascular calcification was comparable in both groups. The iPTH level was found to be an independent risk factor for high intima thickness (correlation coefficient 0.653) (P-value <0.01). Patients with high (≥ 400 pg/mL) iPTH have 8.93 times the risk of developing intimal thickness of ≥ 60 µ m as compared with patients with low (<400 pg/mL) iPTH (P-value <0.05), with 95% confidence interval of 1.27, 62.61. The mean IT of the radial artery significantly correlated with the iPTH level, while vascular calcification was independent of the iPTH level. Hyperparathyroidism is an important cause of ongoing vascular damage and may contribute to higher vascular events in CKD patients.

Comprehensive clinical approach to renal tubular acidosis.

Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and hyperchloremic metabolic acidosis. It is important to understand that despite knowing the disease for 60-70 years, complexities in the laboratory tests and their interpretation still make clinicians cautious to diagnose and label types of tubular disorder. Hence, we are writing this mini-review to emphasize on the step wise approach to RTA with some understanding on its basic etiopathogenesis. This will definitely help to have an accurate interpretation of urine and blood reports in correlation with the clinical condition. RTA can be a primary or secondary defect and results either due to abnormality in bicarbonate ion absorption or hydrogen ion secretion. Primary defects are common in children due to gene mutation or idiopathic nature while secondary forms are more common in adults. We are focusing and explaining here in this review all the clinical and laboratory parameters which are essential for making the diagnosis of RTA and excluding the extrarenal causes of hyperchloremic, normal anion gap metabolic acidosis.

A single arm, prospective, open label, multicentre study for evaluation of efficacy and safety of IV CERA for treatment of chronic renal anaemia in dialysis patients not currently treated with ESA.

INTRODUCTION: CERA, a continuous erythropoietin receptor activator, has reported effective correction of anaemia in international clinical trials. OBJECTIVE: Objective of this study was to evaluate efficacy and safety of CERA in Indian patients who were on dialysis and has not received erythropoiesis stimulating agent (ESA) therapy in last 8 weeks. METHODS: In this open label, single arm, prospective, multi-centre study, 189 patients on dialysis, having Haemoglobin (Hb) between 8 - 10 g/dL and not receiving any ESA for last 8 weeks were included at 14 centers across India. CERA was given intravenous (IV) at the dose of 0.6 microg/kg every two weeks. Primary end point of the study was mean change in Hb concentration from baseline to end of the treatment period (TP) of 16 weeks. RESULTS: Mean change of Hb from baseline to end of TP was 2.11 +/- 1.37 g/dL and 2.08 +/- 1.29 g/dL in intent to treat (ITT) and per protocol (PP) population respectively. Mean time to achieve Hb response was 6.10 +/- 3.87 weeks and 6.16 +/- 3.92 weeks in ITT and PP populations respectively. Out of 68 adverse events (AEs) seen during study period, 33 were serious adverse events (SAEs). As per investigators all SAEs were related to underlying disease and not to the study medication. CONCLUSION: It is concluded that CERA administered once in two weeks in dialysis patients effectively corrected chronic kidney disease (CKD) related anaemia and was well tolerated with no significant untoward effect directly related to drug therapy in Indian population.

Effect of duration, participation rate, and supervision during community rehabilitation on functional outcomes in the first poststroke year in Singapore.

OBJECTIVE: To examine the effect of duration, participation rate, and supervision during community rehabilitation on functional outcome during the first poststroke year. DESIGN: Prospective longitudinal study with interviews at admission, discharge, 1 month, 6 months, and 1 year after discharge. SETTING: Two subacute inpatient rehabilitation units and the community after discharge in Singapore. PARTICIPANTS: Subacute nonaphasic stroke patients (N=215). INTERVENTION: Participation rate in supervised therapy (at an outpatient rehabilitation center) and unsupervised therapy (at home) as defined as proportion of time performing therapy as prescribed by the subacute hospital's multidisciplinary rehabilitation team at discharge. MAIN OUTCOME MEASURE: Performance of activities of daily living as measured by Barthel Index (BI) score at 1 year and improvement in BI scores between adjacent timepoints. RESULTS: At 1 month after discharge, 33.3% were performing supervised therapy more than 25% of the recommended time, and 66.3% of subjects were performing unsupervised therapy more than 75% of the recommended time. On a mixed-model analysis, the independent predictors of lower BI scores were older age, hypertension, greater cognitive impairment, greater depressive symptoms, and greater neurologic impairment. Adjusting for these independent factors, performance of supervised therapy at 1 (ß=8.8; 95% confidence interval [CI], 0.5-17.0; P=.039) and 6 (ß=20.1; 95% CI, 11.0-29.2; P<.001) months postdischarge, but not unsupervised therapy, predicted better BI score at 1 year. Those who performed supervised therapy more than 25% of the recommended time achieved their maximal functional recovery faster than those who performed supervised therapy 25% or less of the recommended time (1 mo vs 6 mo). CONCLUSIONS: Supervised stroke rehabilitation in the community at 1 and 6 months was associated with better functional status at 1 year than unsupervised therapy, and a higher participation rate in supervised therapy was associated with greater and faster functional recovery.

Assessment of Toxicity of Some Penta- and Hexacoordinated Organotin(IV) and Tetracoordinated Tin(II) Complexes of Heterocyclic beta-Diketones.

A number of penta- and hexacoordinated organotin(IV) complexes and tetracoordinated tin(II) complexes of compositions Me2SnCl[RCOC:CON(C6H5)N:CCH3] (where R = - CH(3), -p-ClC(6)H(4), and -C(6)H(5)), Me2Sn[RCOC:CON(C6H5)N:CCH3]2 (where R = -CH(3), and -C(6)H(5)), and Sn(II) [RCOC:CON(C6H5)N:CCH3]2 (where R = -p-ClC(6)H(4) and -C(6)H(5)) were screened for their toxicity against Musca domestica (house fly). In general, organotin(IV) complexes contribute more to the activity than tin(II) complexes.