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Risk of ESRD and Mortality in Kidney and Bladder Stone Formers.

ABSTRACT: RATIONALE & OBJECTIVES:Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers. STUDY DESIGN:Historical matched-cohort study. SETTING & PARTICIPANTS:Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revision codes. Age- and sex-matched individuals who had no codes for stones were the comparison group. PREDICTOR:Stone formers were placed into 5 mutually exclusive categories after review of medical charts: incident symptomatic kidney, recurrent symptomatic kidney, asymptomatic kidney, bladder only, and miscoded (no stone). OUTCOMES:ESRD, mortality, cardiovascular mortality, and cancer mortality. ANALYTICAL APPROACH:Cox proportional hazards models with adjustment for baseline comorbid conditions. RESULTS:Overall, 65 of 6,984 (0.93%) stone formers and 102 of 28,044 (0.36%) non-stone formers developed ESRD over a mean follow-up of 12.0 years. After adjusting for baseline hypertension, diabetes mellitus, dyslipidemia, gout, obesity, and chronic kidney disease, risk for ESRD was higher in recurrent symptomatic kidney (HR, 2.34; 95% CI, 1.08-5.07), asymptomatic kidney (HR, 3.94; 95% CI, 1.65-9.43), and miscoded (HR, 6.18; 95% CI, 2.25-16.93) stone formers, but not in incident symptomatic kidney or bladder stone formers. The adjusted risk for all-cause mortality was higher in asymptomatic kidney (HR, 1.40; 95% CI, 1.18-1.67) and bladder (HR, 1.37; 95% CI, 1.12-1.69) stone formers. Chart review of asymptomatic and miscoded stone formers suggested increased risk for adverse outcomes related to diagnoses including urinary tract infection, cancer, and musculoskeletal or gastrointestinal pain. CONCLUSIONS:The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggests that stone events are associated with kidney injury. The clinical indication for imaging in asymptomatic stone formers, the correct diagnosis in miscoded stone formers, and the cause of a bladder outlet obstruction in bladder stone formers may explain the higher risk for ESRD or death in these groups.

SUBMITTER: Dhondup T

PROVIDER: S-EPMC6252145 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Risk of ESRD and Mortality in Kidney and Bladder Stone Formers.

Dhondup Tsering T Kittanamongkolchai Wonngarm W Vaughan Lisa E LE Mehta Ramila A RA Chhina Jasdeep K JK Enders Felicity T FT Hickson LaTonya J LJ Lieske John C JC Rule Andrew D AD

American journal of kidney diseases : the official journal of the National Kidney Foundation 20180823 6

<h4>Rationale & objectives</h4>Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers.<h4>Study design</h4>Historical matched-cohort study.<h4>Setting & participants</h4>Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revisio ...[more]

PMID: 30146423

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Project description:Background and objectivesPrior work has suggested a higher risk of hypertension in kidney stone formers but lacked disease validation and adjustment for potential confounders. Certain types of stone formers may also be at higher risk of hypertension.Design, setting, participants, & measurementsIn our study, incident symptomatic stone formers in Olmsted County from 2000 to 2011 were manually validated by chart review and age and sex matched to Olmsted County controls. We followed up patients through November 20, 2015. Hypertension was also validated by manual chart review, and the risk of hypertension in stone formers compared with controls was assessed both univariately and after adjusting for comorbidities. The risk of hypertension among different subtypes of stone formers was also evaluated.ResultsAmong 3023 coded stone formers from 2000 to 2011, a total of 1515 were validated and matched to 1515 controls (mean age was 45 years old, and 56% were men). After excluding those with baseline hypertension (20% of stone formers and 18% of controls), 154 stone formers and 110 controls developed hypertension. Median follow-up time was 7.8 years in stone formers and 9.6 years in controls. Stone formers were found to have a higher risk of hypertension compared with controls (hazard ratio, 1.50; 95% confidence interval, 1.18 to 1.92), even after adjusting for age, sex, body mass index, serum creatinine, CKD, diabetes, gout, coronary artery disease, dyslipidemia, tobacco use, and alcohol abuse (hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.21). Results were similar after excluding patients who were ever on a thiazide diuretic (hazard ratio, 1.65; 95% confidence interval, 1.16 to 2.38). Stone composition, radiographic stone burden, number of subsequent stone events, and stone removal surgeries were not associated with hypertension (P>0.05 for all).ConclusionsThe risk of hypertension was higher after the first symptomatic kidney stone event. However, kidney stone severity, type, and treatment did not associate with hypertension.

Project description:BackgroundsPrevious studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).MethodsBiobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.ResultsUrine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies.ConclusionsUrinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

Project description:BACKGROUND:Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low. METHODS:We retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion. RESULTS:Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201?±?89 at baseline to 128?±?88 mmol/d for sodium (p?<?0.0001), and from 5.67?±?3.01 to 4.06?±?2.46 mmol/d (p?<?0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39?±?0.26 vs 0.39?±?0.19 mmol/d, p?=?0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones. CONCLUSION:A diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs.

Dataset Information

Risk of ESRD and Mortality in Kidney and Bladder Stone Formers.

Publications

Risk of ESRD and Mortality in Kidney and Bladder Stone Formers.

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