Gut Microbiota and Uremic Retention Solutes in Adults With Moderate CKD: A 6-Day Controlled Feeding Study.

OBJECTIVE: To determine serum and urine concentrations of the uremic retention solutes (URSs), indoxyl sulfate (IS), p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO), and gut microbiota composition in individuals with moderate chronic kidney disease (CKD) compared with matched adults without CKD in a 6-day controlled feeding study. DESIGN AND METHODS: This study was a secondary analysis in which 8 adults with moderate CKD were matched for age, sex, and race with 8 adults without CKD in a parallel-arm, 6-day controlled feeding study. IS, PCS, and TMAO were quantified using liquid chromatography-mass spectrometry in fecal samples, fasting serum, and fasting spot urine samples collected at the end of the feeding period. RESULTS: Fasting serum URS concentrations were 2.8 to 4.9x higher in CKD compared to controls (all P < .05). No differences were found in the composition of the gut microbiota between patients with and without CKD when analyzing samples for α-diversity, ß-diversity, and only minor abundance differences across taxa were apparent. Estimated glomerular filtration rate (eGFR) was inversely related to each serum URS in the whole cohort (all P < .01). However, within groups the relationships between eGFR and serum URS remained strong for CKD patients for IS and TMAO (both P < .05) but weakened for PCS (P = .10). eGFR was only correlated with urine PCS in the whole cohort (P = .03); within groups, no correlation for eGFR with any urine URS was observed. Only urine TMAO was higher in CKD compared to controls (P < .05). CONCLUSION: Serum URS concentrations are elevated in adults with CKD compared to matched non-CKD adults without differences in gut microbiota composition after consuming the same controlled study diet for 6 days. Future studies are needed to determine if specific dietary components may differentially alter the microbiota and URS.

Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.

We have previously demonstrated that acute ingestion of inorganic nitrate (NO3-)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3- → nitrite (NO2-) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3- increased plasma NO3- and NO2- concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3- and NO2- levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3- supplementation. We conclude that both acute and short-term dietary NO3- supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.

The kidney protects against sepsis by producing systemic uromodulin.

Sepsis is a significant cause of mortality in hospitalized patients. Concomitant development of acute kidney injury (AKI) increases sepsis mortality through unclear mechanisms. Although electrolyte disturbances and toxic metabolite buildup during AKI could be important, it is possible that the kidney produces a protective molecule lost during sepsis with AKI. We have previously demonstrated that systemic Tamm-Horsfall protein (THP; uromodulin), a kidney-derived protein with immunomodulatory properties, falls in AKI. Using a mouse sepsis model without severe kidney injury, we showed that the kidney increases circulating THP by enhancing the basolateral release of THP from medullary thick ascending limb cells. In patients with sepsis, changes in circulating THP were positively associated with a critical illness. THP was also found de novo in injured lungs. Genetic ablation of THP in mice led to increased mortality and bacterial burden during sepsis. Consistent with the increased bacterial burden, the presence of THP in vitro and in vivo led macrophages and monocytes to upregulate a transcriptional program promoting cell migration, phagocytosis, and chemotaxis, and treatment of macrophages with purified THP increases phagocytosis. Rescue of septic THP-/- mice with exogenous systemic THP improved survival. Together, these findings suggest that through releasing THP, the kidney modulates the immune response in sepsis by enhancing mononuclear phagocyte function, and systemic THP has therapeutic potential in sepsis.NEW & NOTEWORTHY Specific therapies to improve outcomes in sepsis with kidney injury have been limited by an unclear understanding of how kidney injury increases sepsis mortality. Here, we identified Tamm-Horsfall protein, known to protect in ischemic acute kidney injury, as protective in preclinical sepsis models. Tamm-Horsfall protein also increased in clinical sepsis without severe kidney injury and concentrated in injured organs. Further study could lead to novel sepsis therapeutics.

Incidence and Importance of Calcium Deposition in Kidney Biopsy Specimens.

INTRODUCTION: Calcification on native kidney biopsy specimens is often noted by pathologists, but the consequence is unknown. METHODS: We searched the pathology reports in the Biopsy Biobank Cohort of Indiana for native biopsy specimens with calcification. RESULTS: Of the 4,364 specimens, 416 (9.8%) had calcification. We compared clinical and histopathology findings in those with calcification (n = 429) compared to those without calcification (n = 3,936). Patients with calcification were older, had more comorbidities, lower estimated glomerular filtration rates (eGFR), were more likely to have hyaline arteriosclerosis, interstitial fibrosis/tubular atrophy, and a primary pathologic diagnosis of acute tubular injury or acute tubular necrosis when compared to patients without calcification. Patients with calcium oxalate deposition alone, compared to calcium phosphate or mixed calcifications, had fewer comorbidities but were more likely to have a history of gastric bypass surgery or malabsorption and take vitamin D. In patients with two or more years of follow-up, multivariate analyses showed the presence of calcification (HR 0.59, 0.38-0.92, p = 0.02) and higher eGFR (HR 0.76, 0.73-0.79, p < 0.001), was associated with decreased likelihood of progressing to end-stage renal disease. The presence of calcification was also associated with a reduced slope/decline in eGFR compared to known biopsy and clinical risk factors for decline in kidney function. We hypothesized this was due to more recoverable acute kidney injury (AKI) and found more severe acute kidney injury network stage in patients with kidney calcification but also greater improvement over time. DISCUSSION/CONCLUSION: In summary, we demonstrated that calcification on kidney biopsy specimens was associated with a better prognosis than those without calcification due to the association with recoverable AKI.

Skeletal Muscle Complications in Chronic Kidney Disease.

PURPOSE OF REVIEW: To provide an overview of the recent literature investigating the pathophysiology of skeletal muscle changes, interventions for skeletal muscle, and effects of exercise in chronic kidney disease (CKD). RECENT FINDINGS: There are multiple CKD-related changes that negatively impact muscle size and function. However, the variability in the assessment of muscle size, in particular, hinders the ability to truly understand the impact it may have in CKD. Exercise interventions to improve muscle size and function demonstrate inconsistent responses that warrant further investigation to optimize exercise prescription. Despite progress in the field, there are many gaps in the knowledge of the pathophysiology of sarcopenia of CKD. Identifying these gaps will help in the design of interventions that can be tested to target muscle loss and its consequences such as impaired mobility, falls, and poor quality of life in patients with CKD.

Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer.

BACKGROUND: Reducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method. METHODS: Patients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP). RESULTS: In total, n=8 patients with CKD (eGFR=29-55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant. CONCLUSIONS: Intestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222.

EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients.

The treatment of hyperphosphatemia remains challenging in patients receiving hemodialysis. This phase 1b study assessed safety and efficacy of EOS789, a novel pan-inhibitor of phosphate transport (NaPi-2b, PiT-1, PiT-2) on intestinal phosphate absorption in patients receiving intermittent hemodialysis therapy. Two cross-over, randomized order studies of identical design (ten patients each) compared daily EOS789 50 mg to placebo with meals and daily EOS789 100 mg vs EOS789 100 mg plus 1600 mg sevelamer with meals. Patients ate a controlled diet of 900 mg phosphate daily for two weeks and began EOS789 on day four. On day ten, a phosphate absorption testing protocol was performed during the intradialytic period. Intestinal fractional phosphate absorption was determined by kinetic modeling of serum data following oral and intravenous doses of 33Phosphate (33P). The results demonstrated no study drug related serious adverse events. Fractional phosphate absorption was 0.53 (95% confidence interval: 0.39,0.67) for placebo vs. 0.49 (0.35,0.63) for 50 mg EOS789; and 0.40 (0.29,0.50) for 100 mg EOS789 vs. 0.36 (0.26,0.47) for 100 mg EOS789 plus 1600 mg sevelamer (all not significantly different). The fractional phosphate absorption trended lower in six patients who completed both studies with EOS789 100 mg compared with placebo. Thus, in this phase 1b study, EOS789 was safe and well tolerated. Importantly, the use of 33P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future phase 2 and phase 3 studies.

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans.

BACKGROUND: Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING), is a rare clinical entity with an unclear pathogenesis. The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes mellitus or other predisposing diagnoses. To achieve insights into its pathogenesis, we queried the clinical, histopathologic and transcriptomic features of ING and nodular diabetic nephropathy (DN). METHODS: All renal biopsy reports accessioned at Indiana University Health from 2001 to 2016 were reviewed to identify 48 ING cases. Clinical and histopathologic features were compared between individuals with ING and DN (n = 751). Glomeruli of ING (n = 5), DN (n = 18) and reference (REF) nephrectomy (n = 9) samples were isolated by laser microdissection and RNA was sequenced. Immunohistochemistry of proline-rich 36 (PRR36) protein was performed. RESULTS: ING subjects were frequently hypertensive (95.8%) with a smoking history (66.7%). ING subjects were older, had lower proteinuria and had less hyaline arteriolosclerosis than DN subjects. Butanoate metabolism was an enriched pathway in ING samples compared with either REF or DN samples. The top differentially expressed gene, PRR36, had increased expression in glomeruli 248-fold [false discovery rate (FDR) P = 5.93 × 10-6] compared with the REF and increased 109-fold (FDR P = 1.85 × 10-6) compared with DN samples. Immunohistochemistry revealed a reduced proportion of cells with perinuclear reaction in ING samples as compared to DN. CONCLUSIONS: Despite similar clinical and histopathologic characteristics in ING and DN, the uncovered transcriptomic signature suggests that ING has distinct molecular features from nodular DN. Further study is warranted to understand these relationships.

Spot Urine Samples to Estimate Na and K Intake in Patients With Chronic Kidney Disease and Healthy Adults: A Secondary Analysis From a Controlled Feeding Study.

OBJECTIVE: The objective of this study was to assess the agreement between estimated 24-hour urinary sodium excretion (e24hUNa) and estimated 24-hour urinary potassium excretion (e24hUK), calculated from a spot urine sample using several available equations and actual sodium and potassium intake from a controlled diet in both healthy participants and those with chronic kidney disease (CKD). DESIGN AND METHODS: This study is a secondary analysis of a controlled feeding study in CKD patients matched to healthy controls. Participants (n = 16) consumed the controlled diet, which provided ∼2400 mg Na/day and ∼3000 mg K/day, for 8 days. On days 7 and 8, participants consumed all meals and collected all urine in an inpatient research setting, and they were discharged on day 9. The day 7 morning spot urine sample was used to calculate e24hUNa and e24hUK, which was compared with known sodium and potassium intake, respectively. RESULTS: Average e24hUNa from the INTERSALT and Tanaka-Na equations were higher than actual sodium intake by 373 mg and 559 mg, respectively, though the differences were not significant. e24hUNa from the Nerbass-SALTED equation in CKD participants was significantly higher than actual sodium intake by ∼2000 mg (P < .001), though e24hUNa from the Nerbass-RRID equation was not different from intake. e24hUK from the Tanaka-K equation was significantly lower than actual potassium intake (P < .001). For both e24hUNa and e24hUK for all participants, agreement with actual intake was poor, and e24hUNa and e24hUK were not correlated with actual sodium or potassium intake, respectively. CONCLUSION: e24hUNa and e24hUK are poor indicators of true sodium and potassium intake, respectively, in both healthy and CKD participants. Findings should be confirmed in larger sample sizes with varying levels of dietary sodium and potassium.

Plant-Based Diets, the Gut Microbiota, and Trimethylamine N-Oxide Production in Chronic Kidney Disease: Therapeutic Potential and Methodological Considerations.

High circulating trimethylamine-N-oxide (TMAO) is associated with an increased risk of cardiovascular disease and mortality in people with chronic kidney disease (CKD). In individuals with CKD, reduced kidney function leads to decreased excretion of TMAO, which results in accumulation in the circulation. Higher circulating TMAO has been linked to higher intake of animal-based foods in omnivorous diets. Thus, plant-based diets have been suggested as an intervention to slow the progression of CKD and reduce cardiovascular risk, perhaps explained in part by reduced TMAO production. This article reviews the current evidence on plant-based diets as a dietary intervention to decrease gut-derived TMAO production in patients with CKD, while highlighting methodological issues that present challenges to advancing research and subsequent translation of this approach. Overall, we find that plant-based diets are promising for reducing gut-derived TMAO production in patients with CKD but that further interventional studies are warranted.

Kidney Histopathology and Prediction of Kidney Failure: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The use of kidney histopathology for predicting kidney failure is not established. We hypothesized that the use of histopathologic features of kidney biopsy specimens would improve prediction of clinical outcomes made using demographic and clinical variables alone. STUDY DESIGN: Retrospective cohort study and development of a clinical prediction model. SETTING & PARTICIPANTS: All 2,720 individuals from the Biopsy Biobank Cohort of Indiana who underwent kidney biopsy between 2002 and 2015 and had at least 2 years of follow-up. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographic variables, comorbid conditions, baseline clinical characteristics, and histopathologic features. OUTCOMES: Time to kidney failure, defined as sustained estimated glomerular filtration rate ≤ 10mL/min/1.73m2. ANALYTICAL APPROACH: Multivariable Cox regression model with internal validation by bootstrapping. Models including clinical and demographic variables were fit with the addition of histopathologic features. To assess the impact of adding a histopathology variable, the amount of variance explained (r2) and the C index were calculated. The impact on prediction was assessed by calculating the net reclassification index for each histopathologic variable and for all combined. RESULTS: Median follow-up was 3.1 years. Within 5 years of biopsy, 411 (15.1%) patients developed kidney failure. Multivariable analyses including demographic and clinical variables revealed that severe glomerular obsolescence (adjusted HR, 2.03; 95% CI, 1.51-2.03), severe interstitial fibrosis and tubular atrophy (adjusted HR, 1.99; 95% CI, 1.52-2.59), and severe arteriolar hyalinosis (adjusted HR, 1.53; 95% CI, 1.14-2.05) were independently associated with the primary outcome. The addition of all histopathologic variables to the clinical model yielded a net reclassification index for kidney failure of 5.1% (P < 0.001) with a full model C statistic of 0.915. Analyses addressing the competing risk for death, optimism, or shrinkage did not significantly change the results. LIMITATIONS: Selection bias from the use of clinically indicated biopsies and exclusion of patients with less than 2 years of follow-up, as well as reliance on surrogate indicators of kidney failure onset. CONCLUSIONS: A model incorporating histopathologic features from kidney biopsy specimens improved prediction of kidney failure and may be valuable clinically. Future studies will be needed to understand whether even more detailed characterization of kidney tissue may further improve prognostication about the future trajectory of estimated glomerular filtration rate.

Increasing Nephrologist Awareness of Symptom Burden in Older Hospitalized End-Stage Renal Disease Patients.

BACKGROUND: End-stage renal disease (ESRD) patients have significant symptom burden. Reduced provider awareness of symptoms contributes to underutilization of symptom management resources. METHOD: We hypothesized that improved nephrologist awareness of symptoms leads to symptom improvement. In this prospective, multicenter interventional study, 53 (age >65) ESRD inpatients underwent symptom assessment using the modified Edmonton Symptom Assessment System (ESAS) at admission and 1-week post-discharge. Physicians caring for the enrollees were asked if they felt their patients would die within the year, and then sequentially randomized to receive the results of the baseline survey (group 1) or to not receive the results (group 2). RESULTS: Fifty-two patients completed the study; 1 died. Baseline characteristics were compared. For 70% of the total cohort, physicians reported that they would not be surprised if their patient died within a year. There was no difference in baseline scores of the patients between the 2 physician groups. Severity ratings were compared between in-hospital and post discharge scores and between physicians who received the results versus those that did not. Total ESAS scores improved more in group 1 (12.9) than in group 2 (9.2; p = 0.04). Among individual symptoms, there was greater improvement in pain control (p = 0.02), and nominal improvement in itching (p = 0.03) in group 1 as compared to group 2. There were 3 palliative care consults. CONCLUSIONS: Our findings reinforce the high symptom burden prevalent in older ESRD patients. The improvement in total scores, and individual symptoms of pain and itching in group 1 indicates better symptom control when physician awareness is increased. Residual symptoms post hospitalization and low utilization of palliative care resources are suggestive of a missed opportunity by nephrologists to address the high symptom burden at the inpatient encounter, which is selective for sick patients and/or indication of inadequacy of dialysis to control these symptoms.

Mobility Impairment in Patients New to Dialysis.

BACKGROUND: Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility impairment, (poor gait speed) in patients incident to dialysis, and changes in gait speed over time in a 2-year longitudinal study. METHODS: One hundred eighty-three patients enrolled within 6 months of dialysis initiation were followed up 6, 12, and 24 months later. Grip strength, health-related quality of life, and comorbidities were assessed at baseline. Outcomes were (a) baseline gait speed and (b) change in gait speed over time. Gait speed was assessed by 4-meter walk. Multivariate linear regression was used to identify risk factors for low gait speed at baseline. For longitudinal analyses, linear mixed effects modeling with gait speed modeled over time was used as the outcome. RESULTS: Participants were 54.7 ± 12.8 years old, 52.5% men, 73.9% black with mean dialysis vintage of 100.1 ± 46.9 days and median gait speed 0.78 (0.64-0.094) m/s. Lower health utility and grip strength, diabetic nephropathy, and walking aids were associated with lower baseline gait speed. Loss of 0.1 m/s gait speed occurred in 24% of subjects at 1 year. In multivariate mixed effects models, only age, walking aid use, lower health utility, and lower handgrip strength were significantly associated with gait speed loss. CONCLUSIONS: In our cohort of incident dialysis patients, overall gait speed is very low and 54.2% of the subjects continue to lose gait speed over 2 years. Older age, lower handgrip strength, and quality of life are risk factors for slowness. Patients at highest risk of poor gait speed can be identified at dialysis initiation to allow targeted implementation of therapeutic options.

Sarcopenia, frailty and cachexia patients detected in a multisystem electronic health record database.

BACKGROUND: Sarcopenia, cachexia and frailty have overlapping features and clinical consequences, but often go unrecognized. The objective was to detect patients described by clinicians as having sarcopenia, cachexia or frailty within electronic health records (EHR) and compare clinical variables between cases and matched controls. METHODS: We conducted a case-control study using retrospective data from the Indiana Network for Patient Care multi-health system database from 2016 to 2017. The computable phenotype combined ICD codes for sarcopenia, cachexia and frailty, with clinical note text terms for sarcopenia, cachexia and frailty detected using natural language processing. Cases with these codes or text terms were matched to controls without these codes or text terms matched on birth year, sex and race. Two physicians reviewed EHR for all cases and a subset of controls. Comorbidity codes, laboratory values, and other coded clinical variables were compared between groups using Wilcoxon matched-pair sign-rank test for continuous variables and conditional logistic regression for binary variables. RESULTS: Cohorts of 9594 cases and 9594 matched controls were generated. Cases were 59% female, 69% white, and a median (1st, 3rd quartiles) age 74.9 (62.2, 84.8) years. Most cases were detected by text terms without ICD codes n = 8285 (86.4%). All cases detected by ICD codes (total n = 1309) also had supportive text terms. Overall 1496 (15.6%) had concurrent terms or codes for two or more of the three conditions (sarcopenia, cachexia or frailty). Of text term occurrence, 97% were used positively for sarcopenia, 90% for cachexia, and 95% for frailty. The remaining occurrences were negative uses of the terms or applied to someone other than the patient. Cases had lower body mass index, albumin and prealbumin, and significantly higher odds ratios for diabetes, hypertension, cardiovascular and peripheral vascular diseases, chronic kidney disease, liver disease, malignancy, osteoporosis and fractures (all p < 0.05). Cases were more likely to be prescribed appetite stimulants and caloric supplements. CONCLUSIONS: Patients detected with a computable phenotype for sarcopenia, cachexia and frailty differed from controls in several important clinical variables. Potential uses include detection among clinical cohorts for targeting recruitment for research and interventions.

Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy.

Hypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine. Increasing scientific evidence has supported the utilization of genomic information to select efficacious antihypertensive therapy and understand hereditary contributors to chronic kidney disease progression. Given the wide array of antihypertensive agents available and diversity of genetic renal disease predictors, a panel-based approach to genotyping may be an efficient and economic means of establishing an individualized blood pressure response profile for patients with various forms of chronic kidney disease and hypertension. In this manuscript, we discuss the validation process of a Clinical Laboratory Improvement Amendments-approved genetic test to relay information on 72 genetic variants associated with kidney disease progression and hypertension therapy. These genomic-based interventions, in addition to routine clinical data, may help inform physicians to provide personalized therapy.

Characterizing Dysgeusia in Hemodialysis Patients.

Dysgeusia (abnormal taste) is common in those with chronic kidney disease and contributes to poor nutritional intake. Previous sensory work has shown that taste improves after dialysis sessions. The goal of this pilot study was to characterize altered taste perceptions in patients on dialysis compared with healthy adults, and to evaluate relationships between serum parameters with taste perceptions. We hypothesized that patients undergoing dialysis would experience blunted taste intensities compared with controls, and that serum levels of potential tastants would be inversely related to taste perception of compounds. Using a cross-sectional design, we carried out suprathreshold sensory assessments (flavor intensity and liking) of tastants/flavors potentially influenced by kidney disease and/or the dialysis procedure. These included sodium chloride, potassium chloride, calcium chloride, sodium phosphate, phosphoric acid, urea, ferrous sulfate, and monosodium glutamate. Individuals on maintenance hemodialysis (n= 17, 10 males, range 23-87 years) were compared with controls with normal gustatory function (n=29, 13 males, range 21-61 years). Unadjusted values for intensity and liking for the solutions showed minimal differences. However, when values were adjusted for participants' perceptions of water (as a control for taste abnormalities), intensity of monosodium glutamate, sodium chloride, and sodium phosphate solutions were more intense for patients on dialysis compared with controls. Some significant correlations were also observed between serum parameters, particularly potassium, for dialysis patients and sensory ratings. These results suggest altered taste perception in patients during dialysis warrants further study.

Chronic kidney disease and peripheral nerve function in the Health, Aging and Body Composition Study.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor mobility. Peripheral nerve function alterations play a significant role in low mobility. We tested the hypothesis that early CKD is associated with altered sensory, motor and autonomic nerve function. METHODS: Participants in the Health, Aging and Body Composition cohort who had kidney function measures in Year 3 (1999-2000) and nerve function measurements at Year 4 (2000-01) were analyzed (n = 2290). Sensory (vibration threshold, monofilament insensitivity to light and standard touch), motor [compound motor action potentials (CMAPs), nerve conduction velocities (NCVs)] and autonomic (heart rate response and recovery after a 400-m walk test) nerve function as well as participant characteristics were compared across cystatin C- and creatinine-based estimated glomerular filtration rate categorized as ≤60 (CKD) or >60 mL/min/1.73 m2 (non-CKD). The association between CKD and nerve function was examined with logistic regression adjusted for covariates. RESULTS: Participants with CKD (n = 476) were older (77 ± 3 versus 75 ± 3 years; P < 0.05) and had a higher prevalence of diabetes (20.6% versus 13.1%; P < 0.001). CKD was associated with higher odds for vibration detection threshold {odds ratio [OR] 1.7 [95% confidence interval (CI) 1.1-2.7]} and light touch insensitivity [OR 1.4 (95% CI 1.1-1.7)]. CMAPs and NCVs were not significantly different between CKD and non-CKD patients. In adjusted analyses, participants with CKD had higher odds of an abnormal heart rate response [OR 1.6 (95% CI 1.1-2.2)] and poor heart rate recovery [OR 1.5 (95% CI 1.1-2.0)]. CONCLUSIONS: CKD is associated with changes in sensory and autonomic nerve function, even after adjustment for demographics and comorbidities, including diabetes. Longitudinal studies in CKD are needed to determine the contribution of nerve impairments to clinically important outcomes.

Pilot Study of the Effects of High-Protein Meals During Hemodialysis on Intradialytic Hypotension in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis (HD) have high protein and energy requirements, and protein-energy wasting is common and associated with poor outcomes. Eating during dialysis may improve nutritional status by counteracting the catabolic effects of HD treatment; but eating during HD may be discouraged because of concerns of postprandial hypotension. However, little data are available to support this practice. In this study, we hypothesized that high-protein meals during HD do not lead to symptomatic intradialytic hypotension events. DESIGN: A 9-week, nonrandomized, parallel-arm study. SETTING: A single in-center HD clinic. SUBJECTS: Eighteen patients undergoing HD from 2 shifts completed the study. Patients were aged 62 ± 16 years with dialysis vintage of 3.4 ± 2.6 years. INTERVENTION: Patients in the intervention group (n = 9) undergoing HD received meals of ∼30 g protein and ∼1/3 daily recommended intakes of sodium, potassium, phosphorus, and fluid during dialysis for 25 consecutive HD sessions. The control group (n = 9) completed all aspects of the study including a visit by study personnel but were not given meals. The 25 consecutive sessions before the start of the intervention/control phase were used as a baseline comparison for each patient. MAIN OUTCOME MEASURE: Symptomatic hypotension event frequency. RESULTS: In the intervention arm, there were 19 symptomatic hypotension events in 5 patients prestudy and 18 events in 6 patients during the study. In the control arm, there were 16 events in 7 patients prestudy and 13 events in 7 patients during the study. Change in the frequency of symptomatic hypotension events from prestudy to during study was not different between groups (P = .71). There was no effect of meals on nutritional status, but patients reported positive attitudes toward receiving meals during dialysis. CONCLUSION: High-protein meals during HD did not increase symptomatic hypotension events. Larger, longer term studies are needed to confirm these results and evaluate whether high-protein meals on dialysis benefit nutritional status and clinical outcomes.

Clinical relevance of sarcopenia in chronic kidney disease.

PURPOSE OF REVIEW: In this article, we review sarcopenia in chronic kidney disease (CKD). We aim to present how definitions of sarcopenia from the general population may pertain to those with CKD, its assessment by clinicians and emerging therapies for sarcopenia in CKD. For this review, we limit our description and recommendations to patients with CKD who are not on dialysis. RECENT FINDINGS: Poorer parameters of lean mass, strength and physical function are associated with worsening patient-centered outcomes such as limiting mobility, falls and mortality in CKD; however, the magnitude of these associations are different in those with and without CKD. Sarcopenia in CKD is a balance between skeletal muscle regeneration and catabolism, which are both altered in the uremic environment. Multiple pathways are involved in these derangements, which are briefly reviewed. Differences between commonly used terms cachexia, frailty, protein-energy wasting, dynapenia and sarcopenia are described. Therapeutic options in predialysis CKD are not well studied; therefore, we review exercise options and emerging pharmacological therapies. SUMMARY: Sarcopenia, now with its own International Classification of Diseases, 10th Revision (ICD-10) code, is of importance clinically and should be accounted for in research studies in patients with CKD. Multiple therapies for sarcopenia are in development and will hopefully be available for our patients in the future.

Diet and Diabetic Kidney Disease: Plant Versus Animal Protein.

PURPOSE OF REVIEW: The goal of this review is to present an overview of the evidence on the effectiveness of plant-based diets in delaying progression of diabetic kidney disease (DKD). RECENT FINDINGS: The ideal quantity of dietary protein has been a controversial topic for patients with DKD. Smaller studies have focused on protein source, plant versus animal, for preventing progression. Limited evidence suggests that dietary patterns that focus on plant-based foods, those that are lower in processed foods, or those that are lower in advanced glycation end products (AGE) may be useful in prevention of DKD progression. Increasing plant-based foods, incorporating diet patterns that limit processed foods, or potentially lowering AGE contents in diets may be beneficial for dietary management of DKD. However, dietary studies specifically targeted at DKD treatment are sparse. Further, large trials powered to assess outcomes including changes in kidney function, end-stage kidney disease, and mortality are needed to provide more substantial evidence for these diets.