Concurrent development of encapsulating peritoneal sclerosis and calciphylaxis in a patient with peritoneal dialysis for end-stage renal disease.

Both encapsulating peritoneal sclerosis (EPS) and calciphylaxis are rare but severe complications involving patients with end-stage renal disease. In this report, we discuss a unique case of a 73-year-old female patient who had undergone 8 years of peritoneal dialysis for IgA nephropathy and concurrently developed these two synchronous complications within 3 months of each other. Diagnosis and management of both conditions were discussed in detail as well as the possible association between the two. With surgical treatment for EPS and measures to minimise bone mineral disorder abnormalities, both complications have been successfully managed to date.

"SHOUT" to improve the quality of care delivered to patients with acute kidney injury at Great Western Hospital.

Acute kidney injury (AKI) affects up to 20% of all patients admitted to hospital, and is associated with a higher risk of adverse clinical outcomes, increased healthcare costs, as well as long term risks of chronic kidney disease and end stage renal failure. The aim of this project was to improve the quality of care for patients with AKI admitted to the acute medical unit (AMU) at the Great Western Hospital (GWH). We assessed awareness and self reported confidence among physicians in our Trust, in addition to basic aspects of care relevant to AKI on our AMU. A multifaceted quality improvement strategy was developed, which included measures to improve awareness such as a Trust wide AKI awareness day, and reconfiguring the admission proforma on our AMU in order to enhance risk assessment, staging, and early response to AKI. Ancillary measures such as the dissemination of flashcards for lanyards containing core information were also used. Follow up assessments showed that foundation year one (FY1) doctors' self reported confidence in managing AKI increased from 2.8 to 4.2, as measured on a five point Likert scale (P=0.0003). AKI risk assessment increased from 13% to 57% (P=0.07) following a change in the admission proforma. Documentation of the diagnosis of AKI increased from 66% to 95% (P=0.038) among flagged patients. Documentation of urine dip results increased from 33% to 73% (P=0.01), in addition to a rise in appropriate referral for specialist input, although this was not statistically significant. Our results suggest that using the twin approaches of improving awareness, and small changes to systemic factors such as modification of the admission proforma, can lead to significant enhancements in the quality of care of patients with AKI.

Serum free light chains and the risk of ESRD and death in CKD.

BACKGROUND AND OBJECTIVES: Associations between inflammation and ESRD and death in chronic kidney disease are well established. However, the potential role of the adaptive immune system is uncertain. We aimed to prospectively study the relevance of the adaptive immune system to ESRD and mortality by measuring monoclonal and polyclonal excesses of highly sensitive serum free light chains (sFLCs). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Three hundred sixty-four patients selected from a nephrology outpatient clinic had kappa and lambda sFLCs concentrations and serum immunofixation electrophoresis measured. Cox regression was used to assess the relevance of monoclonal and polyclonal excess of sFLCs to the incidence of ESRD and death (mean follow-up for death 6.0 years). RESULTS: After adjustment for baseline eGFR, there was no significant association between monoclonal excess of sFLCs and risk of ESRD or mortality. Baseline log κ and log λ concentrations were positively associated with ESRD risk, but these associations seemed to be due to correlations with eGFR (per 1 SD higher concentration: adjusted hazard ratio 1.05 [95% confidence interval 0.88 to 1.26] and 0.99 [0.83 to 1.19], respectively). For mortality, after adjustment for eGFR plus markers of cardiac damage, there was weak evidence of an association with λ, but not κ, sFLC concentration (fully adjusted hazard ratio 1.33 [95% confidence interval 1.05 to 1.67] per 1 SD higher concentration). CONCLUSIONS: Associations between monoclonal and polyclonal excess of sFLCs and risk of ESRD are explained by the correlation between these measures and renal function. We found only weak evidence of an association between polyclonal excess of λ sFLC concentration and mortality.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.

BACKGROUND: Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. METHODS: This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. FINDINGS: 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76-1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60-0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68-0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10,000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). INTERPRETATION: Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. FUNDING: Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.

Prediction of ESRD and death among people with CKD: the Chronic Renal Impairment in Birmingham (CRIB) prospective cohort study.

BACKGROUND: Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study with validation in a separate cohort. SETTING & PARTICIPANTS: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort). FACTORS: 44 baseline characteristics (including 30 blood and urine assays). OUTCOMES: ESRD and all-cause mortality. RESULTS: In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death. LIMITATIONS: Other important factors may have been missed because of limited study power. CONCLUSIONS: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities.

BACKGROUND: This study was designed to examine the hypothesis that the nephrotoxicities caused by cyclosporin and tacrolimus might differ in respect of sodium and potassium handling. METHODS: 125 patients were studied retrospectively for the first 90 days after renal transplantation. Eighty were treated initially with cyclosporin and 45 with tacrolimus. RESULTS: A serum sodium level of <135 mmol/l was present for 542/5171 (10.5%) days under tacrolimus treatment compared with 377/5486 (6.9%) days under cyclosporin treatment (P < 0.0001). Severe hyponatraemia, below 120 mmol/l, was also more prevalent under tacrolimus than cyclosporin treatment, P < 0.025. Nine patients, all receiving tacrolimus, were treated with fludrocortisone for fluid depletion and/or hyponatraemia. Serum potassium levels were higher in tacrolimus-treated patients (P < 0.0001), and subjects with hyponatraemia were more likely to experience hyperkalaemia (P < 0.0001). CONCLUSIONS: Hyponatraemia and hyperkalaemia were more frequent in tacrolimus-treated subjects. Taken together with previous work showing that hyperuricaemia is more frequent with cyclosporin treatment, and hypomagnesaemia with tacrolimus treatment, these findings are consistent with qualitative differences between the nephrotoxicities of cyclosporin and tacrolimus.