Cost-effectiveness of population-based screening for microalbuminuria in people with type 2 diabetes mellitus in India.

OBJECTIVES: Patients with diabetes have a higher risk of developing chronic kidney disease (CKD). Early detection of CKD through microalbuminuria screening, followed by treatment, delays the progression of CKD. We evaluated the cost-effectiveness of population-based screening of microalbuminuria among normotensive type 2 diabetes mellitus patients aged >40 years compared with no screening scenario using a decision tree combined with the Markov model. METHODS: We considered two scenarios: Scenario I - dipstick microalbuminuria followed by spot-urine albumin-creatinine ratio (ACR) and serum creatinine in sequence; Scenario II - spot urine ACR plus serum creatinine. A mathematical cohort of the target population was simulated over a lifetime horizon with an annual cycle. Data for the model were obtained from secondary resources. The incremental cost-effectiveness ratios (ICERs) were estimated for screening scenarios compared to nonscreening scenario, along with sensitivity analyses. RESULTS: The discounted ICER per quality-adjusted life years gained for annual microalbuminuria screening in the normotensive diabetic population in India were ₹ 24,114 (US$ 308) and ₹ 13,790 (US$ 176) for scenarios I and II, respectively. Annual screening by scenarios I and II resulted in a reduction of 180 and 193 end-stage renal disease (ESRD) cases per 100,000 population, respectively, resulting in a cost saving of ₹ 12.3 and 13.3 Crore spent on ESRD management over 10 years. Both scenarios were also cost-effective even at the screening frequencies of 5 and 10 yearly. CONCLUSION: Microalbuminuria screening was cost-effective at the threshold of one-time GDP per capita in India.

Correction of metabolic acidosis improves muscle mass and renal function in chronic kidney disease stages 3 and 4: a randomized controlled trial.

BACKGROUND: Metabolic acidosis (MA) is associated with a loss of muscle mass and faster deterioration of kidney function in patients with chronic kidney disease (CKD). A few single-centre randomized trials have reported favourable outcomes following correction of MA. Additional good quality evidence on the safety and efficacy of alkali supplementation is required in epidemiologically different patient subsets with CKD. METHODS: A single-centre, open-label, randomized, prospective parallel-group study was conducted to assess the effect of correction of MA on body composition and kidney function. A total of 188 patients with CKD stages 3 and 4, with venous bicarbonate levels <22 mEq/L were randomized. The intervention arm received standard care as per Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines along with oral sodium bicarbonate supplementation to maintain venous bicarbonate levels at 24-26 mEq/L, whereas the control group received standard care alone. The mid-arm muscle circumference (MAMC), lean body mass (LBM) and estimated glomerular filtration rate (eGFR) were compared between the groups at the end of 6 months. RESULTS: The intervention arm showed a higher LBM {36.8 kg [95% confidence interval (CI) 36.5-37.1] versus 36 [35.7-36.4]; P = 0.002} and MAMC [22.9 cm (95% CI 22.8-23) versus 22.6 (22.5-22.7); P = 0.001] when compared with the control group. The GFR in the intervention arm was higher [32.74 mL/1.73 m2 (95% CI 31.5-33.9) versus 28.2 (27-29.4); P ≤ 0.001]. A rapid decline in GFR was documented in 39 (41.5%) patients in the control arm and 19 (20.2%) patients in the intervention arm (P = 0.001). CONCLUSIONS: Alkali supplementation to increase venous bicarbonate levels to 24-26 mEq/L is associated with preservation of LBM and kidney function in patients with CKD stages 3 and 4.

Reliability of Anthropometry-Based Equations Compared to Dual Energy Absorptiometry for Assessing Body Composition in Predialysis Chronic Kidney Disease-A Longitudinal Study.

OBJECTIVES: Skinfold thickness measurements for assessing body composition are reported to have good reproducibility compared to the reference method of dual energy absorptiometry (DXA). In the current study, we compared the level of agreement between body composition measured with DXA and skinfold thickness (SFT) in CKD Stage 3 and 4, at 2 occasions, 6 months apart. METHODS: Body composition was assessed in 177 Indian patients with CKD Stage 3 and 4 using DXA and anthropometry (SFT). The body fat mass obtained by the 2 methods was compared by paired t-test, intraclass correlation coefficients, regression analysis, and Bland-Altman plots. A linear regression analysis was done to identify the patient-related parameters which would account for the intermethod differences between DXA and SFT. RESULTS: Compared to DXA, SFT underestimated the fat mass at baseline as well as 6 months [DXA vs. SFT at entry: 15.85 kg (95% confidence interval, CI 15.07-16.65) vs. 13.71 kg (95% CI 13.21-14.32), P < .001; at 6 months: 16.13 (95% CI 15.33-16.93) vs. 13.85 (95% CI 13.25-14.45), P < .001]. The intraclass correlation coefficients at entry and 6 months were 0.894 (0.857-0.921) and 0.896 (0.860-0.923), respectively. The intermethod differences between DXA and SFT at baseline and 6 months were comparable: 2.08 kg (95% CI 1.66-2.5) at baseline versus 2.27 kg (95% CI 1.83-2.71) at 6 months, P = 0.200. Gender and body mass index turned out to be the significant predictors of intermethod differences at base line and exit (P < .001). CONCLUSIONS: SFT-based measurements show good reproducibility compared to DXA over a period of 6 months. However, SFT systematically underestimates the fat mass by 2 Kg compared to DXA.

Subcutaneous phaeohyphomycosis in kidney transplant recipients: A series of seven cases.

BACKGROUND: Superficial and deep fungal infections are more frequent in transplant recipients primarily because of the failure of cell-mediated immunity and lesser amount of antigen-presenting Langerhans cells in their epidermis. Here, we report seven cases of post-renal transplant subcutaneous phaeohyphomycosis, all of which manifested within 1 year after transplantation and were unresponsive to prolonged courses of itraconazole. This is the first case series, to our knowledge, of phaeohyphomycosis in transplant recipients in India. METHOD: We performed a retrospective review of cases of phaeohyphomycosis among kidney transplant recipients for type of transplant, immunosuppression, histopathology, and treatment, with prospective follow-up of healed lesion. RESULTS: An overall incidence of 8.3% was noted, with a median duration of approximately 6 months post transplant to the onset of skin lesion. None of the lesions responded to itraconazole alone and 6/7 lesions were surgically excised. Histopathology showed various lesions and culture could isolate Neocytalidium and Exophiala jeanselmi in two cases. CONCLUSION: Dematiaceous fungi are increasingly implicated in cutaneous lesions in transplant recipients. Histopathology and surgical excision are the appropriate tools for diagnosis and treatment, respectively.

Indian chronic kidney disease study: Design and methods.

AIM: The rate and factors that influence progression of chronic kidney disease (CKD) in developing countries like India are unknown. A pan-country prospective, observational cohort study is needed to address these knowledge gaps. METHODS: The Indian Chronic Kidney Disease (ICKD) study will be a cohort study of approximately 5000 patients with mild to moderate CKD presenting to centres that represent different geographical regions in India. Time to 50% decline in baseline estimated glomerular filtration rate, need of renal replacement therapy or any new cardiovascular disease (CVD) event or death from CVD are the primary end points. VALUE OF STUDY: This study will provide the opportunity to determine risk factors for CKD progression and development of CVD in Indian subjects and perform international comparisons to determine ethnic and geographical differences. A bio-repository will provide a chance to discover biomarkers and explore genetic risk factors.

Body Fat Analysis in Predialysis Chronic Kidney Disease: Multifrequency Bioimpedance Assay and Anthropometry Compared With Dual-Energy X-Ray Absorptiometry.

OBJECTIVES: Body composition analysis is required for accurate assessment of nutritional status in patients with predialysis chronic kidney disease (CKD). The reference method for assessing body fat is dual-energy X-ray absorptiometry (DXA), but it is relatively expensive and often not available for widespread clinical use. There is only limited data on the utility of less expensive and easily available alternatives such as multifrequency bioimpedance assay (BIA) and skinfold thickness (SFT) measurements for assessing body fat in predialysis CKD. The study intends to assess the utility of BIA and SFT in measuring body fat compared to the reference method DXA in subjects with predialysis CKD. METHODS: Body composition analysis was done in 50 subjects with predialysis CKD using multifrequency BIA, SFT, and DXA. The agreement between the body fat percentages measured by reference method DXA and BIA/SFT was assessed by paired t-test, intraclass correlation coefficients (ICCs), regression, and Bland-Altman plots. RESULTS: Percentage of body fat measured by BIA was higher compared to the measurements by DXA, but the difference was not significant (30.44 ± 9.34 vs. 28.62 ± 9.00; P = .071). The ICC between DXA and BIA was 0.822 (confidence interval: 0.688, 0.899; P = .000). The mean values of body fat percentages measured by anthropometry (SFT) was considerably lower when compared to DXA (23.62 ± 8.18 vs. 28.62 ± 9.00; P = .000). The ICC between DXA and SFT was .851 (confidence interval: 0.739, 0.915; P = .000). Bland-Altman plots showed that BIA overestimated body fat by a mean of 1.8% (standard deviation, 6.98), whereas SFT underestimated body fat by 5% (standard deviation, 4.01). Regression plots showed a better agreement between SFT and DXA (R(2) = .79) than BIA (R(2) = .50). Overall, SFT showed better agreement with the DXA. Body mass index (BMI) showed a moderate positive correlation with body fat measured by DXA whereas serum albumin failed to show good correlation. CONCLUSIONS: SFT showed relatively better agreement with the reference method DXA, compared to BIA. SFT can be used as a tool for assessing nutritional status in predialysis patients with CKD.

Acute Interstitial Nephritis Following Snake Envenomation: A Single-Center Experience.

OBJECTIVES: To identify the clinical and histopathological characteristics of patients who develop acute interstitial nephritis (AIN) following snake envenomation. METHODS: A retrospective analysis of patients diagnosed with snake envenomation-induced AIN from October 2013 to November 2014. RESULTS: After snake envenomation, 88 patients developed acute kidney injury (AKI). Biopsies were performed on 7 patients due to nonrecovery of kidney function. Among these, 5 patients had AIN. Thus, AIN accounted for 5.7% of snakebite-related acute kidney injury. All patients had severe envenomation at presentation and had prolonged renal failure. Kidney biopsy found a mixed infiltrate composed of predominantly lymphocytes, with variable proportions of other cells including eosinophils neutrophils and plasma cells. The response rate to corticosteroids was 80%. CONCLUSIONS: AIN after snake bite is not uncommon. AIN needs to be considered in patients with persistent renal failure after snake envenomation. Identifying this complication is of utmost importance because of the potentially reversible nature.

Hypomagnesemia and atherogenic dyslipidemia in chronic kidney disease: surrogate markers for increased cardiovascular risk.

BACKGROUND: Recent reports suggest that 40-70 % chronic kidney disease (CKD) patients receiving dialysis have significant coronary artery disease. Magnesium depletion is being considered as the missing link between the cardiovascular risk factors and atherosclerosis in CKD. The present work aimed to study the association between magnesium status and lipid alterations in pre-dialysis CKD patients attending the Nephrology Clinic in a tertiary care hospital in South India. METHODS: 90 cases of CKD and 90 age and gender matched healthy controls were included in the study. Framingham risk scoring was done and presence of metabolic syndrome was assessed. Lipid profile, serum and urine magnesium, blood glucose, calcium, phosphorus, urea and creatinine levels were assayed in all study subjects. RESULTS: In this study we observed a significantly lower serum magnesium levels and dyslipidemic alterations, a significantly raised total cholesterol and low-density lipoprotein and non-HDL in patients with CKD. We also observed a significant correlation between the lowered serum magnesium concentrations and atherogenic dyslipidemia, suggesting a link to increased cardiovascular risk in CKD patients. CKD patients had higher risk of cardiovascular disease (according to their Framingham risk score), which also showed significant correlation with the hypomagnesaemia. CONCLUSIONS: Our results suggest a strong association of hypomagnesemia and atherogenic dyslipidemia in patients with CKD. This gains particular importance in the high cardiovascular risk-borne CKD patients, as supplementing magnesium would go a long way in reducing the risk of cardiovascular morbidity and mortality in CKD.

Pulmonary-renal syndromes: Experience from an Indian Intensive Care Unit.

BACKGROUND: The etiology of patients presenting with pulmonary-renal syndrome (PRS) to Intensive Care Units (ICUs) in India is not previously reported. AIMS: The aim was to describe the prevalence, etiology, clinical manifestations, and outcomes of PRS in an Indian ICU and identify variables that differentiate immunologic causes of PRS from tropical syndromes presenting with PRS. MATERIALS AND METHODS: We conducted a prospective observational study of all patients presenting with PRS over 1-year. Clinical characteristics of patients with "definite PRS" were compared with those with "PRS mimics". RESULTS: We saw 27 patients with "provisional PRS" over the said duration; this included 13 patients with "definite PRS" and 14 with "PRS mimics". The clinical symptoms were similar, but patients with PRS were younger and presented with longer symptom duration. Ninety-two percent of the PRS cohort required mechanical ventilation, 77% required vasopressors and 61.5% required dialysis within 48 h of ICU admission. The etiologic diagnosis of PRS was made after ICU admission in 61.5%. Systemic lupus erythrematosus (54%) was the most common diagnosis. A combination of biopsy and serology was needed in the majority (69%, 9/13). Pulse methylprednisolone (92%) and cyclophosphamide (61.5%) was the most common protocol employed. Patients with PRS had more alveolar hemorrhage, hypoxemia and higher mortality (69%) when compared to "PRS mimics". CONCLUSION: The spectrum of PRS is different in the tropics and tropical syndromes presenting with PRS are not uncommon. Multicentric studies are needed to further characterize the burden, etiology, treatment protocols, and outcomes of PRS in India.

Herpetic Keratitis Following Treatment of Acute Antibody-Mediated Rejection in a Renal Transplantation Recipient.

We report an incident case of herpetic keratitis in a renal transplant recipient treated for acute renal allograft rejection. A lady in her forties, a renal transplant recipient on treatment for allograft rejection, was referred with mild ocular symptoms in the right eye for two days. On evaluation, she had mild conjunctival hyperemia and extensive herpetic epithelial keratitis involving the limbal and central corneas. The patient healed without sequelae from the antivirals and lubricants. Viral keratitis in immunosuppressed patients should be suspected, even in patients with mild symptoms, as early initiation of treatment can prevent rapid stromal involvement and scarring.

Impact of near-miss event during pregnancy and childbirth on maternal health at 12 months.

OBJECTIVE: To assess the impact of maternal near-miss on late maternal death and the prevalence of hypertension or chronic kidney disease (CKD) and mental health problems at 12 months of follow up. METHODS: This prospective cohort study was conducted in a tertiary hospital in the southeastern region of India from May 2018 to August 2019, enrolling those with maternal near-miss and with follow up for 12 months. The primary outcomes were incidence of late maternal deaths and prevalence of hypertension and CKD during follow up. RESULTS: Incidence of maternal near miss was 6.7 per 1000 live births. Among those who had a near miss, late maternal deaths occurred in 7.2% (95% confidence interval [CI] 3.1%-11.3%); prevalence of CKD was 23.0% (95% CI 16.2%-29.8%), and of hypertension was 56.2% (95% CI 50.5%-66.5%) and only two women had depression on follow up. After adjusting for age, parity, socioeconomic status, gestational age at delivery, hemoglobin levels, and perinatal loss, only serum creatinine was independently associated with late maternal death and CKD on follow up. CONCLUSIONS: Women who survive a life-threatening complication during pregnancy and childbirth are at increased risk of mortality and one or more long-term sequelae contributing to the non-communicable disease burden. A policy shift to increase postpartum follow-up duration, following a high-risk targeted approach after a near-miss event, is needed.

Renal Functional Reserve in Acute Kidney Injury Patients Requiring Dialysis.

The incidence of acute kidney injury (AKI) has increased in the recent past. Patients with AKI have an increased risk of mortality. They are also at increased risk of developing chronic kidney disease (CKD). AKI can lead to irreversible loss of renal function despite complete clinical recovery. Currently, no tools are available to diagnose this subclinical loss of renal function. Renal functional reserve (RFR) can serve as an essential tool for analyzing this subclinical loss of renal function, and patients with loss of RFR post-AKI may be closely followed for the development of CKD. This prospective observational study, conducted at the Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), aimed to investigate RFR in 223 patients with AKI requiring dialysis. The study excluded patients with CKD and obstructive uropathy. Methods included RFR assessment three months post-AKI recovery, utilizing technetium-99m (Tc-99m) diethylenetriaminepentaacetic acid (DTPA) plasma clearance during amino acid infusion. Statistical analyses and logistic regression were applied, receiving ethical approval. Results revealed a high in-hospital mortality rate of 78.02%, associated with elevated Sequential Organ Failure Assessment (SOFA) scores. Among 24 patients with complete AKI recovery, the RFR at three months was 10.06% (interquartile range (IQR) 5.60-20.15), with the measured GFR significantly lower than the estimated glomerular filtration rate (GFR). The study concludes that AKI requiring dialysis is linked to high mortality and emphasizes the predictive value of SOFA scores. Additionally, RFR testing at three months post-recovery provides insights into potential long-term impacts on renal function. This study contributes valuable insights into the prognosis of AKI patients requiring dialysis. It underscores the need for further research on RFR as a diagnostic tool and the lasting consequences of AKI.

Does lung ultrasound-guided ultrafiltration lead to better outcomes in acute kidney injury requiring intermittent hemodialysis: A randomized control trial.

INTRODUCTION: Optimization of ultrafiltration during hemodialysis is a critical parameter in achieving therapeutic efficacy and ensuring hemodynamic stability. While various modalities such as blood volume monitoring, inferior vena cava diameter assessment, natriuretic peptide levels, bioimpedance assay, and lung ultrasound have been widely explored in the context of maintenance hemodialysis, the concept of volume-guided ultrafiltration in dialysis patients with acute kidney injury remains unexplored. METHODS: Adult patients with acute kidney injury requiring dialysis, who were hemodynamically stable and not on ventilator support, without underlying lung pathology or cardiac failure, were randomized into two groups. All patients underwent 28-zone lung ultrasound before dialysis. The ultrafiltration was decided based on the treating physician's clinical judgment in controls. In the intervention group, the ultrafiltration orders prescribed by the treating physician were modified, based on the Kerley B line scores obtained by lung ultrasound. The rest of the dialysis prescriptions were similar. A postdialysis lung ultrasound was done in both groups to assess the postdialysis volume status 30 min after the dialysis session. RESULTS: A total of 74 patients undergoing hemodialysis for acute kidney injury were randomized. The baseline characteristics were comparable except for higher baseline B line score scores in the intervention arm. All patients received similar dialysis prescriptions. The lung ultrasound-guided ultrafiltration arm had a higher change in B line scores (BLS) from baseline (4 [0-9.5] vs. 0 [0-4]; p value 0.004) during the first dialysis session. The predialysis BLS indexed to ultrafiltration (mL/kbw/h) were significantly lower in controls, reflecting a relatively higher rate of ultrafiltration in controls compared with intervention (p = 0.006). The total number of dialysis sessions done in the control and intervention arm were 61 and 59, respectively. Among controls, 23/61 sessions (37.7%) had intradialytic adverse events, whereas, in the intervention arm, only 4/59 sessions (6.7) had any adverse intradialytic events (p < 0.01). CONCLUSION: Lung ultrasound-guided ultrafiltration was associated with a better safety profile, as demonstrated by reduced intradialytic events.

Pre-Transplant Cytokine Levels as Signatures of Microvascular Inflammation in Kidney Allograft Biopsies.

BACKGROUND:  The presence of microvascular inflammation (MVI) characterized by leukocyte margination in the glomeruli (glomerulitis, Banff score 'g') and peritubular capillaries (peritubular capillaritis, Banff score 'ptc') is a hallmark histological feature of antibody-mediated rejection (AMR), even in the absence of circumferential C4d positivity. In this study, we assessed the efficacy of pre-transplant plasma cytokines as an ancillary screening tool to identify MVI in kidney allograft indication biopsies to facilitate better graft survival. METHOD:  This single-center prospective analytical study comprises 38 kidney transplant recipients whose peripheral blood was collected before transplant and assessed for the plasma cytokine concentrations of FOXP3, IL-6, TGF beta, and IL-17 using enzyme-linked immunosorbent assays (ELISA). Histopathological assessment was done in post-transplant indication biopsies, and Banff scores of 'g+ ptc' were calculated to categorize recipients into three MVI groups. The correlational, regression, and ROC curve analyses were used to assess the association and predictive ability of the cytokines with respect to MVI. RESULTS:  In our study cohort, 27 recipients had MVI=0, five had MVI=1, and six had MVI≥2. A significant difference in plasma cytokines was observed between these groups, and we found a strong negative correlation of FOXP3 with MVI, whereas a strong positive correlation of IL-6, TGF beta, and IL-17 was recorded with MVI. We have also assessed the predictive ability of these cytokines, FOXP3, IL-6, TGF-beta, and IL-17, through the ROC curve, which showed an AUC of 0.70, 0.76, 0.84, and 0.72, respectively. CONCLUSION:  Our findings suggest that the pre-transplant levels of cytokines FOXP3, IL-6, TGF-beta, and IL-17 could be measured to identify recipients at risk of post-transplant MVI, which could further serve as an additional tool for effective management of the kidney allograft.

Soluble Tumor Necrosis Factor Receptor 2: A Promising Predictive Biomarker for Renal Dysfunction in Membranous Glomerulonephritis.

Background and objective Membranous glomerulonephritis (MGN) is a common cause of adult nephrotic syndrome. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that signals by attaching to TNF receptors. TNF-α plays a pivotal role in the development and progression of different forms of glomerulonephritis. Several research findings suggest that TNF-α receptors (TNFR1 and TNFR2) are predictors of estimated glomerular filtration rate (eGFR) decline. In light of this, this study aimed to explore the relationship between TNFR2 and eGFR, as well as the predictive role of TNFR2 in eGFR decline in MGN. Methods A total of 50 consecutive patients with a diagnosis of primary MGN based on renal biopsies and clinical workups were included in the study. TNFR2 levels in serum, urine, and gene expression were evaluated at baseline and after three months of follow-up by using enzyme-linked immunosorbent assay (ELISA) kits for TNFR2 (KTE60215, Abbkine, Wuhan, China). Cox regression was employed to determine the predictive significance of TNFR2 in persistent eGFR decline. Additionally, an ROC curve analysis was conducted to assess the prognostic value of TNFR2 in predicting persistent eGFR decline among MGN patients. Results We assessed the levels of inflammatory markers TNF-α and TNFR2, examined their correlation with eGFR and renal injury, and investigated their potential in predicting persistent eGFR. Patients with MGN exhibited elevated levels of TNFR2 in their serum, urine, and gene expression compared to healthy individuals. Additionally, there was a positive correlation between serum TNFR2 and TNF-α, urine protein-creatinine ratio (UPCR), uric acid, and total cholesterol. Conversely, there was a negative correlation with eGFR, serum albumin, and calcium. Serum TNFR2 showed statistical significance in a univariate Cox regression analysis (HR: 1.010, 95% CI: 1.00-1.01, p = 0.045) for predicting a persistent decline in eGFR. However, it did not show significance concerning relapse and remission. An ROC curve was created to assess TNFR2's prognostic potential as a biomarker, demonstrating an AUC of 0.683, with a sensitivity of 68% and specificity of 64%. Conclusions Based on our findings, TNFR2 is a predictive biomarker for eGFR decline in MGN, correlating with renal inflammation and predicting deterioration in renal function. TNFR2 emerges as a promising biomarker for early identification in patients at risk of renal function decline.

Adverse Effects of Tacrolimus and Its Associated Risk Factors in Renal Transplant Recipients.

OBJECTIVES: Tacrolimus, an important constituent of the immunosuppressant regimen for renal transplant recipients, can result in posttransplant diabetes mellitus. The adverse effect profile of tacrolimus is yet to be completely understood. The relationship between the blood level of tacrolimus and development of posttransplant diabetes mellitus has not been clearly elucidated in Indian populations. We conducted this study to investigate the frequency of posttransplant diabetes mellitus and other adverse effects of tacrolimus, to enumerate the risk factors associated with posttransplant diabetes mellitus development, and to correlate the blood levels of tacrolimus with its occurrence. MATERIALS AND METHODS: This prospective observational study included 77 renal transplant patients receiving tacrolimus. The blood sugar levels (fasting and postprandial) were monitored, and patients were asked regularly about the adverse effects of tacrolimus experienced by them for 6 months posttransplant. Trough levels of tacrolimus in blood were correlated with occurrence of posttransplant diabetes mellitus. RESULTS: Posttransplant diabetes mellitus developed in 62.3% (48/77) of renal transplant recipients on a tacrolimus-based regimen. Other adverse effects observed included tremors, diarrhea, alopecia, cyto- megalovirus infection, headache, biopsy-proven calci- neurin inhibitor nephrotoxicity, peripheral neuropathy, and BK virus infection. Higher tacrolimus trough level at month 1 posttransplant was significantly associated with the development of posttransplant diabetes mellitus (adjusted odds ratio = 1.379; 95% CI, 1.02-1.86). The best cutoff of tacrolimus trough level at month 1 posttransplant to reduce the risk of posttransplant diabetes mellitus was 8.1 ng/mL. There was a 5 times increased risk of developing posttransplant diabetes mellitus when tacrolimus trough level at month 1 posttransplant was >8.1 ng/mL (adjusted odds ratio = 5.4; 95% CI, 1.4-19.9). CONCLUSIONS: Posttransplant diabetes mellitus is a common adverse effect of tacrolimus among renal transplant recipients. A trough level >8.1 ng/mL at month 1 posttransplant was an important predictor for posttransplant diabetes mellitus.

Association of elevated extracellular HSP72 in albuminuria with systemic inflammation and disease progression in type 2 diabetic kidney disease.

BACKGROUND: Sub-clinical inflammation in hyperglycemia is tied to the pathogenesis of diabetic kidney disease (DKD). Though well known for its immunostimulatory function, the significance of extracellular heat shock protein 72 (eHSP72) in DKD is not well studied. We aimed to determine the association of extracellular HSP72 with systemic inflammation and the progression of DKD, and explore its possible clinical significance in DKD. METHODS: 160 type 2 diabetic individuals were enrolled in the study. Their anthropometric data, routine biochemical parameters, urinary renal function parameters, and blood count parameters were estimated. Plasma from patients' blood samples were used to estimate HSP72 and interleukin 1ß (IL-1ß) using sandwich immunoassays. RESULTS: Plasma eHSP72 is elevated in DKD. Pairwise comparisons showed the drastic elevation of eHSP72 in the presence of albuminuria. A significant positive relationship was observed between plasma levels of eHSP72 and IL-1ß. eHSP72 levels did not statistically differ between micro and macro-albuminuric DKD. However, it was inversely associated with estimated glomerular filtration rate, the index of disease severity, independent of age, gender, diabetes duration and absolute monocyte count. At a cutoff of 0.52 ng/ml, with sensitivity of 64.1 % and specificity of 69.2 %, plasma eHSP72 differentiated the presence of DKD in type 2 diabetics with statistical significance. CONCLUSION: The positive relationship of eHSP72 and IL-1ß with worsening DKD likely indicates their participation in immunostimulatory pathways of renal fibrosis. eHSP72 may be closely linked to albuminuria-induced tubular injury and likely contributes to fibrotic changes in the progression of DKD. From our study, we infer the possible clinical significance of eHSP72 as a marker of sub-clinical renal damage in DKD, and the implication of IL-1ß-associated mechanisms in DKD progression.

Circulating 18-Glycosyl Hydrolase Protein Chitiotriosidase-1 is Associated with Renal Dysfunction and Systemic Inflammation in Diabetic Kidney Disease.

Introduction: Chitotriosidase-1 (CHIT-1) is a marker of macrophage activation and recently attributed to type 2 diabetes mellitus (T2DM). However, its role in the development and progression of diabetic kidney disease (DKD) has been sparsely discussed in the recent literature. Materials and Methods: In this cross-sectional exploratory study, 81 participants with T2DM were classified into two groups based on the presence of DKD. Their anthropometric, biochemical, and pathological profiles were estimated. Circulatory CHIT-1 concentration was determined using the enzyme-linked immuno-sorbent assay (ELISA) in plasma. Results: CHIT-1 was significantly elevated in diabetic nephropathy, independent of age and gender. It is associated with severity of kidney disease, as assessed using urinary protein-creatinine ratio (uPCR) in a multiple linear regression model, independent of age, gender, diabetes duration, and insulin resistance. CHIT-1 positively predicted the likelihood of DKD in the study population (area under the curve = 0.724, P < 0.05). The duration of diabetes correlated positively with uPCR and negatively with estimated glomerular-filtration rate. Neutrophil-Lymphocyte ratio was elevated in participants with DKD. This well-established marker of systemic inflammation exhibited significant positive association with CHIT-1. Conclusion: Plasma CHIT-1 protein is elevated in DKD and associated with disease progression. It is capable of reflecting disease severity and is closely related to systemic inflammation possibly caused by pro-inflammatory circulatory immune cells.

A Randomized Double-Blind Placebo-Controlled Trial Evaluating the Efficacy of Oral Cholecalciferol in Improving Renal and Vascular Functions in Vitamin D-Deficient Patients With Type 2 Diabetes Mellitus.

This study was performed to evaluate the efficacy of cholecalciferol in improving renal and vascular functions in vitamin D-deficient patients with type 2 diabetes mellitus (T2DM) along with chronic kidney disease (CKD). One hundred patients (18 - 65 years), having T2DM along with CKD (stage IIIA and IIIB) and hypovitaminosis D were randomized (1:1) to receive either oral cholecalciferol 60,000 IU (Group A) or placebo (Group B) weekly for 8 weeks along with standard background treatment. They were followed up for another 24 weeks. Various parameters of renal and vascular functions were compared. Except for serum calcium and phosphate levels which were significantly higher in Group A (p < 0.001), there was no significant difference in any of the biochemical or vascular parameters between the two groups at 8 weeks. There were comparable changes in urinary albumin-creatinine ratio and carotid-femoral pulse wave velocity in the two groups at 8 and 24 weeks. There was no improvement in any of the vascular parameters from the corresponding baseline values in the two groups at 8 and 32 weeks. No improvement in renal and vascular functions was observed following treatment with oral cholecalciferol in patients with T2DM and CKD.