Indranil Dasgupta

BACKGROUND: Pruritus (skin irritation or itching) is common in patients with chronic kidney disease (CKD) stages 4 and 5. It is associated with disrupted sleep, reduced quality of life, depression and increased mortality. A video of a patient describing the symptoms is at vimeo.com/49458473. METHODS: We used gabapentin or pregabalin in 71 consecutive patients, 82% male. 25 had CKD stage 4 or 5, median eGFR = 17, range 9-30; 40 were on haemodialysis; 6 on peritoneal dialysis. Median itch severity score out of 10 = 8, range 6-10; median duration of itching = 6 months, range 0.5-240. Serum calcium ≤2.60 mmol/l (≤10.4 mg/dl) in 87% patients, phosphate ≤1.8 mmol/l (≤5.6 mg/dl) in 75%. 63% had used antihistamines and not gained relief. Starting dose of gabapentin 100 mg after dialysis or daily. Patients intolerant of gabapentin were offered pregabalin, starting dose 25 mg after dialysis or daily. RESULTS: Gabapentin relieved itching in 47 patients (66%). A video of a patient describing the effect is at vimeo.com/49455976. 26 patients (37%) suffered side effects from gabapentin. Of 21 patients who stopped gabapentin due to side effects, 16 started pregabalin. Pregabalin relieved itching in 13 patients (81%). In total, gabapentin or pregabalin relieved itching in 60 patients (85%), median follow-up 2 months (range 1-8 months). Median itch severity out of 10 reduced from 8 to 1. CONCLUSIONS: Gabapentin or pregabalin relieved itching in 85% of 71 consecutively treated CKD patients. Patients should be advised about side effects and the drug initiated at a low dose. Patients intolerant of gabapentin may tolerate pregabalin.

BACKGROUND: Chronic kidney disease (CKD) is associated with reduced health-related quality of life (HRQL). However, the relationship between pre-dialysis CKD, HRQL and clinical outcomes, including mortality and progression to end-stage renal disease (ESRD) is unclear. METHODS: All 745 participants recruited into the Renal Impairment In Secondary Care study to end March 2014 were included. Demographic, clinical and laboratory data were collected at baseline including an assessment of HRQL using the Euroqol EQ-5D-3L. Health states were converted into an EQ-5Dindex score using a set of weighted preferences specific to the UK population. Multivariable Cox proportional hazards regression and competing risk analyses were undertaken to evaluate the association of HRQL with progression to ESRD or all-cause mortality. Regression analyses were then performed to identify variables associated with the significant HRQL components. RESULTS: Median eGFR was 25.8 ml/min/1.73 m2 (IQR 19.6-33.7ml/min) and median ACR was 33 mg/mmol (IQR 6.6-130.3 mg/mmol). Five hundred and fifty five participants (75.7%) reported problems with one or more EQ-5D domains. When adjusted for age, gender, comorbidity, eGFR and ACR, both reported problems with self-care [hazard ratio 2.542, 95% confidence interval 1.222-5.286, p = 0.013] and reduced EQ-5Dindex score [hazard ratio 0.283, 95% confidence interval 0.099-0.810, p = 0.019] were significantly associated with an increase in all-cause mortality. Similar findings were observed for competing risk analyses. Reduced HRQL was not a risk factor for progression to ESRD in multivariable analyses. CONCLUSIONS: Impaired HRQL is common in the pre-dialysis CKD population. Reduced HRQL, as demonstrated by problems with self-care or a lower EQ-5Dindex score, is associated with a higher risk for death but not ESRD. Multiple factors influence these aspects of HRQL but renal function, as measured by eGFR and ACR, are not among them.

Background: Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG. Methods: We conducted a retrospective cohort study on 38 614 incident patients with one or more BIS measurement within 90 days of haemodialysis initiation (1 October 2010 through 28 February 2015). We used fractional polynomial regression to determine the association pattern between FOpre, FOpost and IDWG, and multivariate adjusted Cox models with FO and/or IDWG as longitudinal and time-varying predictors to determine all-cause mortality risk. Results: In analyses using 1-month averages, patients in quartiles 3 and 4 (Q3 and Q4) of FO had an incrementally higher adjusted mortality risk compared with reference Q2, and patients in Q1 of IDWG had higher adjusted mortality compared with Q2. The highest adjusted mortality risk was observed for patients in Q4 of FOpre combined with Q1 of IDWG [hazard ratio (HR) = 2.66 (95% confidence interval 2.21-3.20), compared with FOpre-Q2/IDWG-Q2 (reference)]. Using longitudinal means of FO and IDWG only slightly altered all HRs. IDWG associated positively with FOpre, but negatively with FOpost, suggesting a link with post-dialysis extracellular volume depletion. Conclusions: FOpre and FOpost were consistently positive risk factors for mortality. Low IDWG was associated with short-term mortality, suggesting perhaps an effect of protein-energy wasting. FOpost reflected the volume status without IDWG, which implies that this fluid marker is clinically most intuitive and may be best suited to guide volume management in haemodialysis patients.

BACKGROUND: Cognitive impairment is common among persons with chronic kidney disease (CKD), due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differ by PA. METHODS: We leveraged 3223 participants (≥60 years of age) enrolled in National Health and Nutrition Examination Survey (NHANES, 2011-2014), with at least one measure of objective cognitive function [immediate recall (CERAD-WL), delayed recall (CERAD-DR), verbal fluency (AF), executive function/processing speed (DSST), global (average of four tests) or self-perceived memory decline (SCD)]. We quantified the association between CKD stage {no CKD: estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 and albuminuria [albumin:creatinine ratio (ACR)] <30 mg/g; stages G1-G3: eGFR ≥60 mL/min/1.73 m2 and ACR ≥30 mg/g or eGFR 30-59 mL/min/1.73 m2; stages G4 and G5: eGFR <30 mL/min/1.73 m2} and cognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally representative estimates. We tested whether associations differed by PA [Global Physical Activity Questionnaire, high PA ≥600 metabolic equivalent of task (MET) · min/week versus low PA <600 MET · min/week] using a Wald test. RESULTS: Among NHANES participants, 34.9% had CKD stages G1-G3, 2.6% had stages G4 and G5 and 50.7% had low PA. CKD stages G4 and G5 were associated with lower global cognitive function {difference = -0.38 standard deviation [SD] [95% confidence interval (CI) -0.62 to -0.15]}. This association differed by PA (Pinteraction = 0.01). Specifically, among participants with low PA, those with CKD stages G4 and G5 had lower global cognitive function [difference = -0.57 SD (95% CI -0.82 to -0.31)] compared with those without CKD. Among those with high PA, no difference was found [difference = 0.10 SD (95% CI -0.29-0.49)]. Similarly, the CKD stage was only associated with immediate recall, verbal fluency, executive function and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. CONCLUSIONS: CKD is associated with lower objective cognitive function among those with low but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines.