METHODS: Predialysis CKD patients were included in this cross-sectional study. Patient demographics, medical/medication histories, and laboratory parameters (serum 25-hydroxyvitamin D (25(OH)D), creatinine, phosphate (P), calcium, albumin, and intact-PTH (i-PTH)) were collected and compared among patients with various CKD stages. The association between 25(OH)D and these parameters was determined by multiple linear regression.
RESULTS: A total of 196 patients with mean ± SD eGFR of 26.4 ± 11.2 mL/min/1.73 m2 was included. Vitamin D deficiency (25(OH)D concentration < 15 ng/mL) and insufficiency (25(OH)D concentration 16 - 30 ng/mL) was found in 29.1% and 57.7% of the patients, respectively. Mean ± SD serum 25(OH)D was 20.8 ± 9.3 ng/mL. Female patients had lower vitamin D concentrations than males (16.9 ng/mL vs. 23.9 ng/mL; p < 0.001). Vitamin D levels were also higher in Chinese (22.3 ng/mL) than Malay (17.3 ng/mL) and Indian (13.1 ng/mL) patients (p < 0.05). Nonadjusted analyses showed higher i-PTH concentration in vitamin D deficient patients (p < 0.05).
CONCLUSION: Despite being a sun-rich country all year round, the majority (86.8%) of predialysis CKD patients in Singapore have suboptimal vitamin D status. Lower vitamin D concentrations were found in females and in those with darker skin tone. Vitamin D deficient patients also tended to have higher i-PTH levels.
CASE PRESENTATION: We describe here three cases of type 2 diabetic patients that have rapid renal deterioration with rate of decline 46 - 60 mL/min per 1.73m2 per year. All the patients are heavily nephrotic. All of the renal biopsies done showed the classical diabetic changes, hypertensive changes, diffuse tubulointerstitial damage, and interstitial nephritis. All of the patients admitted to taking various form of traditional medications in hope of curing their renal disease.
CONCLUSION: We wish to highlight that type 2 diabetics with massive nephrotic range proteinuria have enhanced risk of rapid renal function deterioration. The patients should be educated about the risks of rapid renal function deterioration when there is presence of heavy proteinuria. High grade proteinuria is likely to inflict the diffuse tubulointerstitial inflammation. The interstitial nephritis could be further worsened by traditional supplements consumption. Timely health education and advice must be undertaken to retard this unwanted rapid renal disease progression.
METHODOLOGY: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS.
RESULTS: A total of 312 CKD patients with mean eGFR 24.5 ± 11.2 ml/min/1.73 m2were enrolled. Based on OH value ≥7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics.
CONCLUSION: BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients.
BACKGROUND: Data are conflicting on the optimal strategy to reduce CAAKI and related complications after percutaneous coronary intervention (PCI).
METHODS: The PRESERVE (Prevention of Serious Adverse Events Following Angiography) trial used a 2 × 2 factorial design to randomize 5,177 patients with stage III or IV chronic kidney disease undergoing angiography to IV 1.26% sodium bicarbonate or IV 0.9% sodium chloride and 5 days of oral acetylcysteine or placebo. A subgroup analysis was conducted of the efficacy of these interventions in patients who underwent PCI during the study angiographic examination. The primary endpoint was a composite of death, need for dialysis, or persistent kidney impairment at 90 days; CAAKI was a secondary endpoint.
RESULTS: A total of 1,161 PRESERVE patients (mean age 69 ± 8 years) underwent PCI. The median estimated glomerular filtration rate was 50.7 ml/min/1.73 m2 (interquartile range: 41.7 to 60.1 ml/min/1.73 m2), and 952 patients (82%) had diabetes mellitus. The primary endpoint occurred in 15 of 568 patients (2.6%) in the IV sodium bicarbonate group and 24 of 593 patients (4.0%) in the IV sodium chloride group (odds ratio: 0.64; 95% confidence interval: 0.33 to 1.24; p for interaction = 0.41) and in 23 of 598 patients (3.8%) in the acetylcysteine group and 16 of 563 patients (2.8%) in the placebo group (odds ratio: 1.37; 95% confidence interval: 0.71 to 2.62; p for interaction = 0.29). There were no significant between-group differences in the rates of CAAKI.
CONCLUSIONS: Among patients with CKD undergoing PCI, there was no benefit of IV sodium bicarbonate over IV sodium chloride or of acetylcysteine over placebo for the prevention of CAAKI or intermediate-term adverse outcomes.
METHODS: A total 621 patients with estimated glomerular filtration rate (eGFR) of 15-59ml/min/1.73m(2) (CKD stage 3 & 4) were selected and followed up for 10 years or until ESRD or death, whichever occurred first. Subjects who did not meet inclusion criteria were excluded (n=1474).
RESULTS: Annual cumulative decline in eGFR was 3.01±0.40 ml/min/1.73m(2) . Overall disease progression was observed in 60% patients while 18% died. Among patients with CKD stage 3, 21% progressed to stage 4, 10% to stage 5ND (non-dialysis) and 31% to RRT while mortality was observed in 16% patients. On the other hand, 8% patients with CKD stage 4 progressed to stage 5ND, 31% to RRT and mortality was observed in 24% cases. Patients with CVD, higher systolic blood pressure, elevated phosphate levels, heavy proteinuria, microscopic hematuria and use of diuretics were more likely to develop ESRD. Advancing age, low eGFR, low systolic blood pressure, low hemoglobin and baseline diabetes were found to be significant predictors of mortality while being female reduced risk of mortality.
CONCLUSION: Our data suggest that, in this CKD cohort, patients were more likely to develop ESRD than death. Prime importance should be given to mild forms of CKD to retard and even reverse CKD progression.
METHODS: A postal questionnaire was sent to 349 patients registered at the Sheffield Kidney Institute with chronic kidney disease but not on renal replacement therapy (RRT). The questionnaire incorporated three validated forms: kidney disease quality-of-life short form (KDQOL SF1.3) to assess QOL; nine-item patient health questionnaire (PHQ9) to screen for depression; multidimensional scale of perceived social support (MSPSS) to evaluate perceived social support; as well as a novel genetic psychosocial risk instrument (GPRI-ADPKD) designed to study the specific psychosocial impact of coping with a diagnosis of ADPKD.
RESULTS: The overall response rate was 53%. Patients with a lower estimated glomerular filtration rate (<30 mL/min) or larger kidneys (mean length on ultrasound ≥17 cm) reported reduced QOL and increased psychosocial risk. Clinically significant depression was reported in 22% and 62% felt guilty about passing ADPKD on to their children. In multivariate analysis, female gender was associated with overall poorer psychosocial well-being, whereas increasing age, lower kidney function, larger kidneys and loss of a first degree relative from ADPKD were additional risk factors for QOL, depression or psychosocial risk, respectively.
CONCLUSIONS: Our results reveal a significantly poorer QOL and increasing psychosocial risk with markers of disease progression in patients, particularly women, with ADPKD prior to starting RRT. The future management strategy of ADPKD should address these issues and provide for better individual and family support throughout the patient journey.
METHODS: DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18-75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin-angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694.
FINDINGS: Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730-1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI -16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by -6·6 mL/min per 1·73 m2 (-9·0 to -4·2; p<0·0001) at week 6. This reduction was fully reversible within 6 weeks after dapagliflozin discontinuation. Compared with placebo, bodyweight was reduced by 1·5 kg (0·03-3·0; p=0·046) with dapagliflozin; changes in systolic and diastolic blood pressure and concentrations of neurohormonal biomarkers did not differ significantly between dapagliflozin and placebo treatment. The numbers of patients who had one or more adverse events during dapagliflozin treatment (17 [32%] of 53) and during placebo treatment (13 [25%] of 52) were similar. No hypoglycaemic events were reported and no deaths occurred.
INTERPRETATION: 6-week treatment with dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in mGFR and a reduction in bodyweight. Long-term clinical trials are underway to determine whether SGLT2 inhibitors can safely reduce the rate of major clinical kidney outcomes in patients with chronic kidney disease with and without diabetes.
FUNDING: AstraZeneca.
METHODS: Utilizing the Malaysian National Cardiovascular Disease Database-Percutaneous Coronary Intervention (NCVD-PCI) registry data from 2007 to 2014, STEMI patients treated with percutaneous coronary intervention (PCI) were stratified into presence (GFR
METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.
RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.
CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.
METHODS: Planned analysis of data was collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Patients missing preoperative creatinine data were excluded. We used multivariable logistic regression to examine the relationships among preoperative creatinine-based estimated glomerular filtration rate (eGFR), postoperative AKI, and hospital mortality, accounting for the effects of age, major comorbid diseases, and nature and severity of surgical intervention on outcomes. We similarly modeled preoperative associations of AKI. Data are presented as n (%) or odds ratios (ORs) with 95% confidence intervals.
RESULTS: A total of 36,357 patients were included, 743 (2.0%) of whom developed AKI with 73 (9.8%) deaths in hospital. AKI affected 73 of 196 (37.2%) of all patients who died. Mortality was strongly associated with the severity of AKI (stage 1: OR, 2.57 [1.3-5.0]; stage 2: OR, 8.6 [5.0-15.1]; stage 3: OR, 30.1 [18.5-49.0]). Low preoperative eGFR was strongly associated with AKI. However, in our model, lower eGFR was not associated with increasing mortality in patients who did not develop AKI. Conversely, in older patients, high preoperative eGFR (>90 mL·minute·1.73 m) was associated with an increasing risk of death, potentially reflecting poor muscle mass.
CONCLUSIONS: The occurrence and severity of AKI are strongly associated with risk of death after surgery. However, the relationship between preoperative renal function as assessed by serum creatinine-based eGFR and risk of death dependent on patient age and whether AKI develops postoperatively.