Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes.

INTRODUCTION: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. METHODS: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. RESULTS: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (-0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. -1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43-0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57-0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74-1.15, P = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68-1.33, P = 0.76). CONCLUSION: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants.

Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.

BACKGROUND AND OBJECTIVES: The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Families with autosomal dominant interstitial kidney disease were referred for genetic analysis over a 14-year period. Families without UMOD or REN mutations prospectively underwent genotyping for the presence of the MUC1 mutation. Clinical characteristics were retrospectively evaluated in individuals with the MUC1 mutation and historically affected individuals (persons who were both related to genetically affected individuals in such a way that ensured that they could be genetically affected and had a history of CKD stage IV or kidney failure resulting in death, dialysis, or transplantation). RESULTS: Twenty-four families were identified with the MUC1 mutation. Of 186 family members undergoing MUC1 mutational analysis, the mutation was identified in 95 individuals, 91 individuals did not have the mutation, and111 individuals were identified as historically affected. Individuals with the MUC1 mutation suffered from chronic kidney failure with a widely variable age of onset of end stage kidney disease ranging from 16 to >80 years. Urinalyses revealed minimal protein and no blood. Ultrasounds of 35 individuals showed no medullary cysts. There were no clinical manifestations of the MUC1 mutation detected in the breasts, skin, respiratory system, or gastrointestinal tract. CONCLUSION: MUC1 mutation results in progressive chronic kidney failure with a bland urinary sediment. The age of onset of end stage kidney disease is highly variable, suggesting that gene-gene or gene-environment interactions contribute to phenotypic variability.

Anatomic and physiologic changes of the aging kidney.

Aging is associated with structural and functional changes in the kidney. Structural changes include glomerulosclerosis, thickening of the basement membrane, increase in mesangial matrix, tubulointerstitial fibrosis and arteriosclerosis. Glomerular filtration rate is maintained until the fourth decade of life, after which it declines. Parallel reductions in renal blood flow occur with redistribution of blood flow from the cortex to the medulla. Other functional changes include an increase in glomerular basement permeability and decreased ability to dilute or concentrate urine.

Clinical performance and skill retention after simulation-based education for nephrology fellows.

We previously demonstrated that simulation-based education (SBE) improved temporary hemodialysis catheter (THDC) insertion skills by nephrology fellows. SBE, featuring deliberate practice and rigorous achievement standards, was a powerful method to enhance THDC insertion skills in nephrology fellows. However, experts have called for further research to evaluate skill transfer from the simulated environment to actual clinical care and skill retention. This is a prospective observational cohort study of THDC insertion skills. Twelve nephrology fellows from three academic centers in Chicago were evaluated using a skills checklist from July 2008 to June 2009. Simulator-trained fellows were tested after the SBE intervention and expected to meet or exceed a minimum passing score (MPS) set by an expert panel. To assess transfer of skill to clinical care, three simulator-trained fellows were assessed at 6 months on actual patient THDC insertions using the checklist. To assess retention of skill, 11 of 12 simulator-trained fellows were reassessed at 1 year using the checklist and central venous catheter simulator. Outcomes were determined by THDC insertion skill performance. Simulator-trained fellows scored similarly during 6-month THDC insertions on actual patients and immediate posttest (M = 86.2%, SD = 22.3% vs. M = 93.5%, SD = 5.3%, p = 0.32). However, 1 year after SBE, simulated THDC insertion scores were significantly lower than at immediate posttest (M = 73.4%, SD = 22.2% vs. M = 93.5%, SD = 5.3%, p = 0.01). Our results show that nephrology fellows who completed SBE displayed high levels of performance during THDC insertions on actual patients 6 months later. At 1 year, there was statistically significant skills decay. We recommend booster training at 6 months.

Lithium-associated kidney microcysts.

Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33-62.5% of the patients undergoing lithium therapy. MR imaging is highly capable of defining renal morphological features and has been demonstrated to be superior to US and CT scan for the visualization of small renal cysts. The microcysts are found in both cortex and medulla, particularly in the regions with extensive atrophy and fibrosis, and can be multiple and bilateral. They tend to be sparse and do not normally exceed 1-2 mm in diameter. The renal microcysts in the image here reported are subtle, but consistent with lithium-induced chronic nephropathy. An MRI of the kidneys provides noninvasive evidence that strengthens the diagnosis of lithium-induced nephropathy.