Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to develop the novel analytical approach and to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Patient Perception of Plant Based Diets for Kidney Disease.

OBJECTIVE: Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and comorbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. The objective of this study was to understand nephrology patients' familiarity, perception, and use of plant-based diets. DESIGN & METHODS: A survey was shared via the National Kidney Foundation's social media channels. Analysis included 844 responses. Survey items were evaluated with descriptive statistics. Differences across items were determined using chi-square tests. RESULTS: Most respondents were 61-70 years of age (26.7%, n = 225), female (56.5%, n = 477) and achieved a Bachelor's or advanced degree (49.9%, n = 421). The majority of respondents suffered from nondialysis-dependent CKD (34%) or received a kidney transplant (34%). About half (45%) of respondents were familiar with plant-based diets and most (58%) were aware that plant-based diets can improve CKD. Twenty-two percent reported following some version of a vegetarian diet, and 29% reported "eating less meat". Respondents were not confident (Mdn = 2, IQR = 2, on a scale of 1-5) in their ability to plan a balanced plant-based meal, and were moderately confident that a plant-based diet could help blood pressure (Mdn = 3, IQR = 2) and slow progression of CKD (Mdn = 3, IGR = 2). Family eating preference, meal planning skills, preference for meat, figuring out what is healthy to eat, food cost, time constraints, and ease of cooking were rated as equal barriers to following a plant-based diet (Mdn = 3). A sample meal plan, individual counseling session with a Registered Dietitian Nutritionist (RDN), handouts, and cooking classes were resources rated most helpful to transition to a plant-based diet (Mdn = 4). CONCLUSION: Approximately half of respondents were aware that plant-based diets can be beneficial for CKD. Many patients are following a vegetarian or plant-based eating pattern. More research should be done to see how effective RDNs are in educating and moving patients toward a plant-based eating pattern, as they are an underutilized resource in the CKD population.

A Randomized Trial Evaluating the Use of a Smart Water Bottle to Increase Fluid Intake in Stone Formers.

OBJECTIVE: The aim of this study is to evaluate if the use of a smart water bottle improves urine volume in stone forming patients. METHODS: Adults with nephrolithiasis and low urine volume (<1.5 L) documented on a 24-hour urinalysis (24 hr U) were randomized to receive either standard dietary recommendations to increase fluid intake (DR arm), or DR and a smart water bottle (HidrateSpark®; Hydrate Inc., Minneapolis, MN) that recorded fluid intake, synced to the user's smartphone, and provided reminders to drink (SB arm). Participants completed baseline surveys assessing barriers to hydration. They then repeated a 24 hr U and survey at 6 and 12 weeks, respectively. RESULTS: Eighty-five subjects (44 DR, 41 SB) were enrolled. The main baseline factor limiting fluid intake was not remembering to drink (60%). Follow-up 24 hr Us were available for 51 patients. The mean increase in volume was greater in the SB arm (1.37 L, 95% confidence interval -0.51 to 3.25) than the DR arm (0.79 L, 95% confidence interval -1.15 to 2.73) (P = .04). A smaller percentage of subjects in the SB arm reported not remembering to drink as the main factor limiting fluid intake in the follow-up questionnaire compared to baseline (45.4% vs. 68.4%, P < .05). This was not true for the DR arm (40.0% vs. 51.2%, P = .13). CONCLUSIONS: Difficulty remembering to drink is a barrier to achieving sufficient fluid intake in stone formers. The use of a smart bottle was associated with greater increases in 24 hr U volumes and less difficulty remembering to drink.

Plant-based Diets in Kidney Disease: Nephrology Professionals' Perspective.

OBJECTIVE: Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and co-morbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. However, it is unclear how often plant-based diets are recommended to patients with kidney disease. The objective of this study was to understand nephrology professionals' familiarity, perception, and recommendation of plant-based diets to people with kidney disease. DESIGN AND METHODS: A survey to understand perception of recommendation of plant-based diets for patients with CKD was developed. Nephrology professionals from the National Kidney Foundation's member directory were e-mailed a link to complete the survey online. This directory includes professionals who work in a variety of nephrology settings, including both CKD and end-stage renal disease care. Survey items were evaluated with descriptive statistics. Differences across items were determined using chi-square tests and t-tests. RESULTS: A total of 3,901 professionals were sent the survey, and 644 completed the survey. A majority were dietitians (58%) and worked in dialysis clinics (54%). Most (88%) had heard of using plant-based diets for kidney disease treatment, and a majority (88%) believed it could improve CKD management, cardiovascular disease (90%), hypertension (90%), diabetes (84%), high cholesterol (90%), and obesity (84%). Dietitians were more likely to report plant-based diets as beneficial for each health condition (P < .05). Professionals were most confident that a plant-based diet could help control hypertension (3.75 ± 0.99 on a scale of 1-5), compared with delaying progression of CKD (3.68 ± 1.15) or treating acidosis (3.68 ± 1.13). Dietitians felt more confident in their ability to plan a balanced plant-based diet compared with other specialties (3.49 vs. 2.74, P < .001). CONCLUSION: Nephrology professionals who work in nondialysis-dependent CKD settings, and those who work with patients on dialysis, are aware of the benefits of plant-based diets in kidney disease. However, plant-based diets are not routinely being offered as a treatment option. Nephrology practices should work to increase dietitian referrals to offer patients support in transitioning to a plant-based diet.

Cystinuria: Review of a Life-long and Frustrating Disease.

Cystinuria, accounting for about 1-2% of kidney stones in adults, carries significant morbidity beginning at a young age [1]. Cystine stone formers have more stone events compared to other stone formers, as well as more surgical interventions, potentially contributing to faster progression to chronic kidney disease (CKD), and end-stage kidney disease (ESKD) [2]. Successful medical therapy for cystine stone formers may be limited by adherence to the extensive lifestyle changes and the adverse side effect profiles of some interventions, leading to decreased quality of life for these patients relative to other stone formers.

Racial Differences in Risk Factors for Kidney Stone Formation.

BACKGROUND AND OBJECTIVES: Incidence of kidney stone disease is rising. It is not known whether mechanisms of stone formation differ across racial groups. Our objective was to identify differing lithogenic risk factors across racial groups in idiopathic nephrolithiasis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study evaluating metabolic risk factors in black and age-matched white idiopathic stone formers at our tertiary referral center. We compared serum and urine metabolic risk factors pre- and post-treatment across racial groups using analysis of covariance. Generalized linear modeling was used to build regression models for risk of stone formation in both groups. RESULTS: Among 117 black and 172 white stone formers, urine volume was lower in black stone formers (1.4±0.8 versus 2.0±0.8 L/d, P<0.001). Urine calcium was lower in black stone formers (116±70 versus 217±115 mg/d, P<0.001). Supersaturations for calcium oxalate were similar among the groups, whereas calcium phosphate supersaturation was higher in white stone formers, and uric acid supersaturation was higher in black stone formers. Electrolyte free water clearance was significantly lower in black stone formers (207±780 versus 435±759 ml/d, P=0.02). In the subgroup of 77 black patients and 107 white patients with post-treatment evaluations, urine volume rose significantly and similarly in both groups. Urine sodium was unchanged in whites but increased in blacks by 40 mmol/d (95% confidence interval, 32 to 48 mmol/d). Electrolyte free water clearance remained lower in black stone formers (385±891 versus 706±893 ml/d, P=0.02). Post-treatment supersaturations were similar across the groups except for calcium phosphate, which improved with treatment in whites. CONCLUSIONS: Black stone formers have lower 24-hour urine calcium excretion and urine volume. Increases in urine volume with treatment were associated with increased solute, but not free water, excretion in black stone formers.

Evaluation and Medical Management of Patients with Cystine Nephrolithiasis: A Consensus Statement.

Purpose: Cystinuria is a genetic disorder with both autosomal recessive and incompletely dominant inheritance. The disorder disrupts cystine and other dibasic amino acid transport in proximal tubules of the kidney, resulting in recurrent kidney stone formation. Currently, there are no consensus guidelines on evaluation and management of this disease. This article represents the consensus of the author panel and will provide clinicians with a stepwise framework for evaluation and clinical management of patients with cystinuria based on evidence in the existing literature. Materials and Methods: A search of MEDLINE®/PubMed® and Cochrane databases was performed using the following key words: "cystine nephrolithiasis," "cystinuria," "penicillamine, cystine," and "tiopronin, cystine." In total, as of May 2018, these searches yielded 2335 articles, which were then evaluated for their relevance to the topic of evaluation and management of cystinuria. Evidence was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Twenty-five articles on the topic of cystinuria or cystine nephrolithiasis were deemed suitable for inclusion in this study. The literature supports a logical evaluation process and step-wise treatment approach beginning with conservative measures: fluid intake and dietary modification. If stone formation recurs, proceed to pharmacotherapeutic options by first alkalinizing the urine and then using cystine-binding thiol drugs. Conclusions: The proposed clinical pathways provide a framework for efficient evaluation and treatment of patients with cystinuria, which should improve overall outcomes of this rare, but highly recurrent, form of nephrolithiasis.

Effectiveness of Treatment Modalities on Kidney Stone Recurrence.

Nephrolithiasis is highly prevalent across all demographic groups in the Western world and beyond, and its incidence rates are rising. In addition to the morbidity of the acute event, stone disease often becomes a lifelong problem that requires preventative therapy to diminish ongoing morbidity. Across the majority of stone types, increased fluid intake and targeted dietary modifications are mainstays of therapy. Specific dietary interventions associated with reduced calcium stone risk include adequate dietary calcium intake and restriction of sodium, protein, and oxalate intake, among others. Pharmaceutical therapy may be required if lifestyle changes are insufficient to minimize risk of stone recurrence, and must be targeted to the specific metabolic abnormalities portending risk for a given patient. Therapeutic options for idiopathic calcium stone disease include thiazides, citrate salts, and uric acid-lowering agents. Alkali salts are also the treatment of choice for uric acid stone disease. Management of struvite stone disease is largely surgical, but acetohydroxamic acid is a proven second line therapy. Cystinuria requires lifestyle modifications and may call for thiol-binding agents. Significant heterogeneity of the clinical population with stone disease has previously limited opportunities for large randomized controlled trials. However, as clinical phenotypes and genotypes are increasingly clarified, there are mounting opportunities for targeted randomized controlled trials in stone prevention. In the meantime, the currently available evidence for both lifestyle and pharmacologic interventions is reviewed herein.

Do kidney stone formers have a kidney disease?

Nephrolithiasis is a highly prevalent disorder affecting approximately one in eleven people and is associated with multiple complications including hypertension, cardiovascular disease, and chronic kidney disease. Significant epidemiologic associations with chronic kidney disease and ESRD have been noted and are reviewed herein, but debate persists in the literature as to whether kidney stone formation is a pathogenic process contributing to kidney disease. Corroborating evidence supporting the presence of kidney disease in stone formers includes the variability of renal function by stone type, the positive association of stone size with renal dysfunction, the presence of markers of renal injury in the urine of even asymptomatic stone formers, and direct evidence of renal tissue injury on histopathology. Proposed pathogenic mechanisms include recurrent obstruction and comorbid conditions such as recurrent urinary tract infections and structural abnormalities. Recent work evaluating the renal histopathology of different groups of stone formers adds further granularity, suggesting variability in mechanisms of renal injury by stone type and confirming the pathogenic effects of crystal formation. Genetic abnormalities leading to stone formation including cystinuria and primary hyperoxaluria, among others, contribute to the burden of disease in the stone-forming population.

Kidney stones: an update on current pharmacological management and future directions.

INTRODUCTION: Kidney stones are a common problem worldwide with substantial morbidities and economic costs. Medical therapy reduces stone recurrence significantly. Much progress has been made in the last several decades in improving therapy of stone disease. AREAS COVERED: This review discusses i) the effect of medical expulsive therapy on spontaneous stone passage, ii) pharmacotherapy in the prevention of stone recurrence and iii) future directions in the treatment of kidney stone disease. EXPERT OPINION: Fluid intake to promote urine volume of at least 2.5 L each day is essential to prevent stone formation. Dietary recommendations should be adjusted based on individual metabolic abnormalities. Properly dosed thiazide treatment is the standard therapy for calcium stone formers with idiopathic hypercalciuria. Potassium alkali therapy is considered for hypocitraturia, but caution should be taken to prevent potential risk of calcium phosphate stone formation. For absorptive hyperoxaluria, low oxalate diet and increased dietary calcium intake are recommended. Pyridoxine has been shown effective in some cases of primary hyperoxaluria type I. Allopurinol is used in calcium oxalate stone formers with hyperuricosuria. Treatment of cystine stones remains challenging. Tiopronin can be used if urinary alkalinization and adequate fluid intake are insufficient. For struvite stones, complete surgical removal coupled with appropriate antibiotic therapy is necessary.

Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones.

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range.

Recent advances in the rapidly evolving field of fibroblast growth factor 23 in chronic kidney disease.

PURPOSE OF REVIEW: In recent years, there has been an increasing awareness of the central regulatory role of fibroblast growth factor 23 (FGF23) in mineral metabolism and its particular prominence in patients with chronic kidney disease (CKD). RECENT FINDINGS: FGF23 is a powerful predictor of adverse clinical outcomes in CKD that appears to be superior to existing mineral metabolism markers such as serum phosphate and parathyroid hormone. Interesting new data suggest a central role of bone health in the regulation of FGF23 secretion, whereas another important new study reported that virtually all circulating FGF23 in advanced renal failure is biologically intact. Finally, new data demonstrate the ability to alter FGF23 levels using common CKD therapies such as phosphate binders, active vitamin D, and cinacalcet. SUMMARY: Although FGF23 was originally discovered in studies of rare diseases, we expect that its primary utility in mainstream clinical practice will ultimately lie in the management of CKD. Emerging data highlight the potential of FGF23 as a novel diagnostic to identify CKD patients at the highest risk for disease progression, cardiovascular disease, and death, and those who might benefit from early phosphorus-related therapies before the onset of overt hyperphosphatemia.

Pancreatic cancer patients who smoke and drink are diagnosed at younger ages.

BACKGROUND & AIMS: Cigarette smoking is an established risk factor for pancreatic cancer, but there is conflicting evidence regarding the effects of alcohol consumption. The effects of cigarettes and alcohol on age of sporadic pancreatic cancer diagnosis have not been examined; we evaluated the independent and synergistic effects of lifetime cigarette smoking and alcohol consumption on age at pancreatic cancer diagnosis in the United States. METHODS: We analyzed data on cigarette smoking and alcohol consumption from the IMPAC Services, Inc Cancer Information Resource File (CIRF), collected from June 1, 1993, to December 31, 2003, for 29,239 reported, histologically confirmed cases of pancreatic adenocarcinoma. We also analyzed data on cigarette smoking and alcohol consumption for 820 histologically confirmed cases of pancreatic adenocarcinoma from the University of Michigan Pancreatic Cancer Registry (UMPCR), collected from January 2004 to October 2007. RESULTS: Current cigarette smokers were diagnosed at significantly younger ages than never smokers, according to data from the CIRF and UMPCR (8.3 and 6.3 y, respectively); the UMPCR data indicated dose effects. Past and current alcohol consumption were associated with younger age at diagnosis in both databases. Current smokers who were current drinkers were diagnosed significantly earlier (CIRF, 10.2 y; UMPCR, 8.6 y) than abstainers. Past cigarette smoking was associated modestly with younger diagnosis age. CONCLUSIONS: Cigarette smoking and alcohol consumption were associated with younger age at pancreatic cancer presentation and have a combined effect on diagnosis age. Past cigarette smoking is less influential. Smoking cessation programs could help prevent pancreatic cancer.

Impact of ergocalciferol treatment of vitamin D deficiency on serum parathyroid hormone concentrations in chronic kidney disease.

BACKGROUND: Vitamin D deficiency is highly prevalent and associated with secondary hyperparathyroidism in patients with chronic kidney disease (CKD). The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend treatment of vitamin D deficiency starting with CKD stage 3, though no data are available showing an impact on serum parathyroid hormone (PTH) concentrations. The goal of this analysis, therefore, was to determine the effect of ergocalciferol treatment on plasma PTH concentrations in vitamin D-deficient patients with stage 3 and stage 4 CKD. METHODS: A prospective, nonrandomized observational analysis was conducted in an academic community hospital CKD clinic. Fifty-two patients with stage 3 or stage 4 CKD with vitamin D deficiency and elevated PTH concentrations received ergocalciferol dosed per a modified K/DOQI guidelines protocol and adjusted every 3 months. Serum PTH, 25-vitamin D, 1,25-vitamin D, calcium, phosphorus, and albumin levels were drawn at initiation of therapy and repeated every 3 months. RESULTS: The mean 25-vitamin D levels normalized in patients with stage 3 and 4 CKD, with values of 31.6 +/- 2.2 ng/ml (78.8 +/- 5.49 nmol/l) and 35.4 +/- 1.9 ng/ml (88.4 +/- 4.74 nmol/l), respectively (p < 0.0001). A median decrease in PTH concentrations of 13.1 and 2.0% was noted in patients with stage 3 and stage 4 CKD, respectively (p = 0.041, p = nonsignificant). CONCLUSIONS: Ergocalciferol therapy is a reasonable initial therapy for vitamin D deficiency associated with elevated PTH levels in stage 3 CKD. It does not appear to have equivalent benefits in stage 4 CKD.

Associations between the age at diagnosis and location of colorectal cancer and the use of alcohol and tobacco: implications for screening.

BACKGROUND: Individualizing recommendations for colorectal cancer (CRC) screening intervals and modalities requires accurate risk assessment. Although hereditary predisposition is commonly used, the effect of exogenous risk factors has remained largely unexplored. To address this, we analyzed the age at presentation and location of CRC in relation to alcohol and tobacco use. METHODS: We queried the IMPAC Medical Registry Services Cancer Information Resource File for CRCs diagnosed between June 1, 1993, and December 31, 2003. Subjects were classified as current, past, or never users of alcohol and tobacco. A logistic regression model for location of CRC and a linear regression model for age at diagnosis were constructed using these explanatory variables along with gender, race, and insurance status. RESULTS: Our data set consisted of 161 172 patients with CRC. Current drinking, smoking, and smoking plus drinking were associated with younger ages at onset of CRC (adjusted age difference, 5.2, 5.2, and 7.8 years, respectively; P<.001 for all). A distal location of CRC was more likely to occur in current drinkers (odds ratio, 1.192; 95% confidence interval, 1.15-1.23) and smokers (odds ratio, 1.164; 95% confidence interval, 1.12-1.21). Colorectal cancer in men tended to occur earlier (adjusted age difference, 1.9 years; P<.001) and have a distal predominance (odds ratio, 1.42; P<.001) compared with women. The smoking but not the drinking effect size was greater in women than in men (adjusted age difference, 2.6 years; P<.001). CONCLUSIONS: Alcohol use, tobacco use, and male gender were associated with earlier onset and a distal location of CRC. If confirmed, these factors should guide recommendations regarding initiation of CRC screening and, possibly, choice of techniques.

Bone disease after kidney transplantation.

Advances in immunosuppressive therapy have allowed for enhanced allograft survival in kidney transplantation. With this increasing success of transplantation, however, has come a greater appreciation of subsequent complications, such as bone and mineral disease. In patients with chronic kidney disease who are awaiting transplantation, disorders in mineral metabolism and renal osteodystrophy are an essentially universal finding, and several different pathophysiologic mechanisms are believed to contribute to the development of these disorders.

Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and doxercalciferol.

INTRODUCTION: Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients. METHODS: Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for 6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline and monitored every 2 weeks. A linear regression analysis of percent change in iPTH values by dose group was performed to determine the conversion factor. RESULTS: 27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum phosphorus, and CaxP were similar among the treatment groups. Linear regression analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected serum calcium, phosphorus, CaxP product, as well as incidence of hypercalcemia, hyperphosphatemia and CaxP >50 were similar for all groups. CONCLUSION: In patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55-60% of the paricalcitol dose results in comparable inhibition of PTH.