Search

Secondary hyperparathyroidism is associated with mortality in patients undergoing maintenance dialysis treatment. We studied 515 male US veterans with chronic kidney disease, who were not yet on dialysis, to see what outcomes were associated with secondary hyperparathyroidism in this population. Relationships between intact parathyroid hormone levels and all-cause mortality along with the composite of mortality or incidence of dialysis were measured in unadjusted and adjusted Cox models for case-mix and laboratory variables. Elevated parathyroid hormone levels above the upper limit compared to the lower limit of the normal range were significantly associated with mortality after adjustments. Higher intact parathyroid hormone levels in the upper limit of normal were significantly associated with higher mortality overall and showed similar trends in subgroups of patients with stage 3 and stage 4-5 chronic kidney disease and with higher and lower serum calcium and phosphorus levels. Similar associations were found with the composite outcome of mortality or dialysis. Our study shows that secondary hyperparathyroidism is independently associated with higher mortality in patients with chronic kidney disease but not yet on dialysis.

Replacement of activated vitamin D has been the cornerstone of therapy for secondary hyperparathyroidism (SHPT). Recent findings from several large observational studies have suggested that the benefits of vitamin D receptor activators (VDRA) may extend beyond the traditional parathyroid hormone (PTH)-lowering effect, and could result in direct cardiovascular and metabolic benefits. The advent of several new analogs of the activated vitamin D molecule has widened our therapeutic armamentarium, but has also made therapeutic decisions more complicated. Treatment of SHPT has become even more complex with the arrival of the first calcium-sensing receptor (CSR) agonist (cinacalcet hydrochloride) and with the uncovering of novel mechanisms responsible for SHPT. We provide a brief overview of the physiology and pathophysiology of SHPT, with a focus on vitamin D metabolism, and discuss various practical aspects of VDRA therapy and its reported association with survival in recent observational studies. A detailed discussion of the available agents is aimed at providing the practicing physician with a clear understanding of the advantages or disadvantages of the individual medications. A number of open questions are also analyzed, including the present and future roles of CSR agonists and 25(OH) vitamin D replacement.

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

Anemia is a common complication of chronic kidney disease (CKD), but the outcomes associated with lower hemoglobin (Hgb) levels in patients with CKD not yet on dialysis are not well characterized. Analyses exploring outcomes associated with a single baseline Hgb value also do not account for the longitudinal variation of this measure. After collecting all Hgb measurements (N=17 194, median (range): 12 (1-168)) over a median follow-up period of 2.1 years in a historical prospective cohort of 853 male US veterans with CKD Stages 3-5 not yet on dialysis, we examined the association of time-averaged Hgb levels with predialysis all-cause mortality, end-stage renal disease (ESRD), and a composite end point of both. Kaplan-Meier survival analysis and Cox models adjusted for age, race, body mass index, smoking status, blood pressure, diabetes mellitus, cardiovascular disease, categories of estimated glomerular filtration rate, serum concentrations of albumin and cholesterol, and proteinuria were examined. Lower time-averaged Hgb was associated with significantly higher hazard of the composite end point (hazard ratio (95% confidence interval) in the adjusted model for time-averaged Hgb of 130 g/l: 2.57 (1.85-3.58), 1.97 (1.45-2.66), 1.19 (0.86-1.63), P(trend)

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the Vitality score between baseline and Week 28. Outcome superiority was tested (1-sided alpha level of 0.025). Overall, 614 participants with non-dialysis-dependent CKD were randomized. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A significantly greater proportion of participants receiving daprodustat showed a 1 g/dl or greater increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a clinically and statistically significant 5.4 point Week 28 AMD increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m 2 or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m 2 ) and change in eGFR (<-3, -3 to <0 [reference], and ≥0 mL/min/1.73m 2 /year) were examined in propensity-matched patients based on their likelihood to initiate biologic treatment, using Cox models and multinomial logistic regression models, respectively. Among 20,757 patients, 4,617 started biologic therapy. In the propensity-matched cohort, patients treated (versus not treated) with biologic agents had a lower risk of incident CKD (hazard ratios 0.95, 95% confidence interval [0.82-1.10] and 0.71 [0.53-0.94] for decrease in eGFR under 60 and under 45 mL/min/1.73m 2 , respectively) and progressive eGFR decline (multinomial odds ratios [95% CI] for eGFR slopes <-3 and ≥0 [versus -3 to <0] mL/min/1.73m 2 /year, 0.67 [0.58-0.79] and 0.76 [0.69-0.83], respectively). A significant deceleration of eGFR decline was also observed after biologic administration in patients treated with biologics (-1.0 versus -0.4 [mL/min/1.73m 2 /year] before and after biologic use). Thus, biologic agent administration was independently associated with lower risk of incident CKD and progressive eGFR decline., (Published by Elsevier Inc.)

Most patients with end-stage renal disease in the United States are initiated on thrice-weekly hemodialysis (HD) regimens. However, an incremental approach to HD may provide several patient benefits. We tested whether initiation of incremental HD does or does not compromise survival compared with a conventional HD regimen. The survival of 434 incremental, 50,162 conventional, and 160 frequent HD patients were compared using Cox regression analysis after matching for demographic and comorbid factors in a longitudinal national cohort of adult incident HD patients enrolled between January 2007 and December 2011. Sensitivity analysis included adjustment for residual kidney function. After adjustment for residual kidney function, all-cause mortality was not significantly different in the incremental compared with conventional HD group (hazard ratio 0.88, 95% confidence interval 0.72-1.08), but was higher in the frequent compared with the conventional HD group (hazard ratio, 1.56, 95% confidence interval 1.21-2.03). The comorbidity burden modified the association of treatment frequency and mortality, with higher comorbidity associated with higher mortality in the incremental HD group (hazard ratio, 1.77, 95% confidence interval 1.20-2.62) for a Charlson Comorbidity Index of ≥5. Thus, among incident HD patients with low or moderate comorbid disease, survival was similar for patients initiated on an incremental or conventional HD regimen. Clinical trials are needed to examine the safety and effectiveness of incremental HD and the selected patient populations who may benefit from an incremental approach to HDs initiation., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

It is not clear to what extent changes in blood pressure (BP) during hemodialysis affect or predict survival. Studying comparative outcomes of BP changes during hemodialysis can have major clinical implications including the impact on management strategies in hemodialysis patients. Here we undertook a retrospective cohort study of 113,255 hemodialysis patients over a 5-year period to evaluate an association between change in BP during hemodialysis and mortality. The change in BP was defined as post-hemodialysis minus pre-hemodialysis BP, and mean of BP change values during the hemodialysis session was used as a mortality predictor. The patients' average age was 61 years old and consisted of 45% women, 32% African-Americans and 58% diabetics. Over a median follow-up of 2.2 years, a total of 53,461 (47.2%) all-cause and 21,548 (25.7%) cardiovascular deaths occurred. In a fully adjusted Cox regression model with restricted cubic splines, there was a U-shaped association between change in systolic BP and all-cause mortality. Post-dialytic drops in systolic BP between -30 and 0 mm Hg were associated with greater survival, but large decreases of systolic BP (more than -30 mm Hg) and any increase in systolic BP (over 0 mm Hg) were related to increased mortality. Peak survival was found at a change in systolic BP of -14 mm Hg. The U-shaped association was also found for cardiovascular mortality. Thus, modest declines in BP after hemodialysis are associated with the greatest survival, whereas any rise or large decline in BP is associated with worsened survival.

To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m(2). After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22-24.99 kg/m(2), overweight patients (BMI 25-29.99 kg/m(2)), mild obesity patients (BMI 30-34.99 kg/m(2)), and moderate-to-severe obesity patients (BMI 35 kg/m(2) and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF.

The survival of patients with ESRD living in various geographic regions is strikingly different. Efforts to determine the reasons behind this observation have been hampered by difficulties in adjusting for many characteristics that are inherently different in patient populations living on different continents. The mortality rate for the general population in a given region could be used to adjust for risk factors that would be otherwise difficult to quantify.