Adherence to Plant-Based Diets and Risk of CKD Progression and All-Cause Mortality: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in individuals with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,539 participants with CKD recruited between 2003-2008 into the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Responses on the Diet History Questionnaire were used to calculate scores for the overall plant-based diet index, healthy plant-based diet index, and unhealthy plant-based diet index. OUTCOME: (1) CKD progression defined as≥50% estimated glomerular filtration rate decline from baseline or kidney replacement therapy (dialysis, transplant) and (2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models to compute hazard ratios and 95% confidence intervals adjusting for lifestyle, socioeconomic, and clinical covariates. RESULTS: There were 977 CKD progression events and 836 deaths during a median follow-up period of 7 and 12 years, respectively. Participants with the highest versus lowest adherence to overall plant-based diets and healthy plant-based diets had 26% (HR, 0.74 [95% CI, 0.62-0.88], P trend<0.001) and 21% (HR, 0.79 [95% CI, 0.66-0.95], P trend=0.03) lower risks of all-cause mortality, respectively. Each 10-point higher score of unhealthy plant-based diets was modestly associated with a higher risk of CKD progression (HR, 1.14 [95% CI, 1.03-1.25) and all-cause mortality (HR, 1.11 [95% CI, 1.00-1.23). LIMITATIONS: Self-reported diet may be subject to measurement error. CONCLUSIONS: Adherence to an overall plant-based diet and a healthy plant-based diet is associated with a reduced risk of all-cause mortality among individuals with CKD. An unhealthy plant-based was associated with an elevated risk of CKD progression and all-cause mortality. PLAIN-LANGUAGE SUMMARY: Plant-based diets are healthful dietary patterns that have been linked to a lower risk of chronic diseases. However, the impact of plant-based diets on clinical outcomes in patients with chronic kidney disease (CKD) is not well established. In 2,539 individuals with CKD, we examined the associations of adherence to 3 different types of plant-based diets with the risks of CKD progression and all-cause mortality. We found that following an overall plant-based diet and a healthy plant-based diet was associated with a lower risk of all-cause mortality. By contrast, following an unhealthy plant-based diet was associated with a higher risk of CKD progression and all-cause mortality. These results suggest that the quality of plant-based diets may be important for CKD management.

Ultraprocessed Foods and Kidney Disease Progression, Mortality, and Cardiovascular Disease Risk in the CRIC Study.

RATIONALE & OBJECTIVE: Ultraprocessed foods are widely consumed in the United States and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adults with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed baseline dietary questionnaires. EXPOSURE: Ultraprocessed food intake (in servings per day) classified according to the NOVA system. OUTCOMES: CKD progression (≥50% decrease in estimated glomerular filtration rate [eGFR] or initiation of kidney replacement therapy), all-cause mortality, and incident CVD (myocardial infarction, congestive heart failure, or stroke). ANALYTICAL APPROACH: Cox proportional hazards models adjusted for demographic, lifestyle, and health covariates. RESULTS: There were 1,047 CKD progression events observed during a median follow-up of 7 years. Greater ultraprocessed food intake was associated with higher risk of CKD progression (tertile 3 vs tertile 1, HR, 1.22; 95% CI, 1.04-1.42; P=0.01 for trend). The association differed by baseline kidney function, such that greater intake was associated with higher risk among people with CKD stages 1/2 (eGFR≥60mL/min/1.73m2; tertile 3 vs tertile 1, HR, 2.61; 95% CI, 1.32-5.18) but not stages 3a-5 (eGFR<60mL/min/1.73m2; P=0.003 for interaction). There were 1,104 deaths observed during a median follow-up of 14 years. Greater ultraprocessed food intake was associated with higher risk of mortality (tertile 3 vs tertile 1, HR, 1.21; 95% CI, 1.04-1.40; P=0.004 for trend). LIMITATIONS: Self-reported diet. CONCLUSIONS: Greater ultraprocessed food intake may be associated with CKD progression in earlier stages of CKD and is associated with higher risk of all-cause mortality in adults with CKD. PLAIN LANGUAGE SUMMARY: Ultraprocessed foods are industrial formulations produced using ingredients and processes that are not commonly used in culinary preparations and contain few, if any, intact unprocessed foods. Ultraprocessed foods are widely consumed in the United States, and high intakes of such foods have been linked to cardiovascular disease, kidney disease, and mortality in the general population. In this study, we found that greater intake of ultraprocessed foods was associated with higher risk of kidney disease progression and mortality in adults with chronic kidney disease. Our findings suggest that patients with kidney disease may benefit from greater consumption of fresh, whole, and homemade or hand-prepared foods and fewer highly processed foods.

Emerging Preventive Strategies in Chronic Kidney Disease: Recent Evidence and Gaps in Knowledge.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is increasingly prevalent worldwide and is associated with increased cardiovascular risk. New therapeutic options to slow CKD progression and reduce cardiovascular morbidity and mortality have recently emerged. This review highlights recent evidence and gaps in knowledge in emerging CKD preventive strategies. RECENT FINDINGS: EMPA-Kidney trial found that empagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i) led to 28% lower risk of progression of kidney disease or death from cardiovascular causes, compared to placebo. This reinforced the previous findings from DAPA-CKD and CREDENCE trials and led to inclusion of SGLT2i as the cornerstone of CKD preventive therapy in both diabetic and non-diabetic CKD. Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, slowed diabetic kidney disease progression by 23% compared to placebo in a pool analysis of FIDELIO-DKD and FIGARO-DKD trials. Non-pharmacological interventions, including low protein diet, and early CKD detection and risk stratification strategies based on novel biomarkers have also gained momentum. Ongoing efforts to explore the wealth of molecular mechanisms in CKD, added to integrative omics modeling are well posed to lead to novel therapeutic targets in kidney care. While breakthrough pharmacological interventions continue to improve outcomes in CKD, the heterogeneity of kidney diseases warrants additional investigation. Further research into specific kidney disease mechanisms will facilitate the identification of patient populations most likely to benefit from targeted interventions.

Concomitant monoclonal immunoglobulin deposition disease and crystalglobulin-induced nephropathy with a membranoproliferative pattern of glomerular injury
.

Monoclonal immunoglobulin paraproteins can deposit in the kidney in variable forms and eliciting differing patterns of injury. Crystalglobulin-induced nephropathy is a rare form of monoclonal immunoglobulin deposition in the kidney, characterized by glomerular capillary endoluminal crystalline material evident by light and electron microscopy that exhibits immunoglobulin restriction via immunofluorescence studies. We present a case of a patient with acute kidney injury, and a subsequent kidney biopsy notably revealed concurrent monoclonal immunoglobulin deposition disease (MIDD) and crystalglobulin-induced nephropathy secondary to an IgM/κ monoclonal protein that resulted in a membranoproliferative pattern of glomerular injury. The two process were distinctly evident by ultrastructural crystalline and non-crystalline (as seen with cases of more conventional MIDD) deposits in the glomeruli. The paraprotein constituency is novel (IgM/κ) for crystalglobulin-induced nephropathy (prior cases exhibited IgG/κ restriction) as was the finding of the two monoclonal immunoglobulin deposition processes contributing to development of an active glomerulitis characterized by a membranoproliferative pattern of glomerular injury (crystalglobulin-induced nephropathy has not been associated with an active glomerulitis before).

Orthostatic hypotension, orthostatic hypertension, and ambulatory blood pressure in patients with chronic kidney disease in CRIC.

BACKGROUND: Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown. METHODS: CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP. RESULTS: Of the 1386 participants (age: 58 ±â€Š10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (ß = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (ß = -4 [-7.2, -0.5]) and diastolic WCE (ß = -6 [-8.1, -4.2]). CONCLUSION: Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes.

Isolated Diastolic Hypertension and Kidney and Cardiovascular Outcomes in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: The clinical significance of isolated diastolic hypertension in patients with chronic kidney disease (CKD) is unclear. We assessed the prevalence of isolated diastolic hypertension and its association with adverse kidney and cardiovascular outcomes in participants in the Chronic Renal Insufficiency Cohort (CRIC) study. Study Design: Prospective cohort study. Setting & Population: CRIC study participants with complete baseline data on systolic blood pressure (SBP) and diastolic BP (DBP) (N=5,621). Exposure: Isolated diastolic hypertension defined as SBP ≤ 130 mm Hg and DBP >80 mm Hg. Reference Group: Normotension, defined as SBP ≤ 130 mm Hg and DBP ≤ 80 mm Hg. Outcomes: Composite kidney events (50% decline in estimated glomerular filtration rate or onset of kidney failure), composite cardiovascular events (myocardial infarction, heart failure, stroke, or peripheral arterial disease), and all-cause mortality. Analytical Approach: Cox proportional hazards models adjusted for demographic, health behavior, and clinical covariates. Results: Of the 5,621 participants, 347 (6.2%) had isolated diastolic hypertension. Among the 347 participants with isolated diastolic hypertension, there was no association between isolated diastolic hypertension and the composite kidney outcome (HR, 1.17; 95% CI, 0.93-1.47; P = 0.18), composite cardiovascular events (HR, 0.91; 95% CI, 0.65-1.27; P = 0.58), or all-cause mortality (HR, 0.82; 95% CI, 0.57-1.19; P = 0.30). Limitations: Older age of cohort and low number of participants of Asian ethnicity limit generalizability of findings. A relatively small sample size is inadequate to detect modest associations with outcomes. Conclusions: Isolated diastolic hypertension was not associated with the risk of adverse kidney and cardiovascular events in participants with CKD. Plain Language Summary: Clinicians frequently encounter patients with kidney disease who have controlled systolic blood pressure (BP) but high diastolic BP and do not know whether they should intensify BP treatment in an attempt to control the diastolic BP. We examined whether having controlled systolic BP but uncontrolled diastolic BP leads to worse heart and kidney outcomes in patients with chronic kidney disease. We did not find any such association. However, our study was relatively small and had a number of limitations. Till larger studies confirm or refute this finding, we recommend not increasing blood pressure medications to improve the diastolic BP control if the systolic BP is already well controlled in patients with chronic kidney disease.

Orthostatic Hypertension and Intensive Blood Pressure Control; Post-Hoc Analyses of SPRINT.

We evaluated the association between orthostatic hypertension and cardiovascular outcomes and the effect of intensive blood pressure (BP) control on cardiovascular outcomes in patients with orthostatic hypertension. Post hoc analyses of the SPRINT (Systolic Blood Pressure Intervention Trial) data were conducted; orthostatic hypertension was defined as increase in systolic BP≥20 mm Hg or increase in diastolic BP≥10 mm Hg with standing. Of 9329 participants, 1986 (21.2%) had orthostatic hypertension at baseline. Within the intensive treatment group, participants with orthostatic hypertension were at higher risk of developing the composite cardiovascular outcome (hazard ratio, 1.44 [95% CI, 1.1-1.87], P=0.007) compared with participants without orthostatic hypertension. Within the standard treatment group, there were no significant differences in cardiovascular outcome between participants with and without orthostatic hypertension. In participants with orthostatic hypertension, there was no statistically significant difference in risk of the composite cardiovascular outcome between the intensive and the standard BP treatment group (hazard ratio, 1.07 [95% CI, 0.78-1.47], P=0.68). In participants without orthostatic hypertension at baseline, the intensive treatment group was associated with a lower risk of the composite cardiovascular outcome (hazard ratio, 0.67 [95% CI, 0.56-0.79], P<0.0001). Orthostatic hypertension was associated with a higher risk of cardiovascular outcomes in the intensive and not in the standard treatment group; intensive treatment of BP did not reduce the risk of cardiovascular outcomes compared with standard treatment in patients with orthostatic hypertension. These post hoc analyses are hypothesis generating and will need to be confirmed in future studies.

Correlation between Dt/V derived from ionic dialysance and blood-driven Kt/V of urea in African-American hemodialysis patients, based on body weight and ultrafiltration volume.

BACKGROUND: The Dt/V obtained by using ionic dialysance (D) as a surrogate for urea clearance (K) is a well-validated adjunct measure of hemodialysis adequacy, with a variable level of correlation with urea-based Kt/V. However, this correlation has not been examined based on patients' body size and ultrafiltration (UF) volume during the dialysis session. METHODS: Simultaneous evaluations of online Dt/V and single-pool variable-volume urea Kt/V were made. Patients were categorized into three subgroups based on their weight (<60, 60-80 and ≥80 kg), body mass index (<25, 25-30 and >30 kg/m2) and UF volume (<1.5, 1.5-3 and >3 L). The correlation between Dt/V and Kt/V was evaluated for the entire cohort per dialysis session in each subgroup. RESULTS: Mean Kt/V was greater than the mean Dt/V (1.72 versus 1.50, P < 0.001), with an overall correlation r value of 0.602. This correlation was stronger in the medium weight group versus lower and higher weights. The correlation between Dt/V and Kt/V was inversely related to the UF volume (r = 0.698, 0.621 and 0.558 for those with UF volume of <1.5, 1.5-3.0 and >3 L, respectively). A total of 99.3% of patients with Dt/V of >1.2 also had Kt/V >1.2 and 9.5% of those with Dt/V <1.2 had their Kt/V <1.2. CONCLUSIONS: There is a moderate degree of correlation between Dt/V and Kt/V in African-American hemodialysis patients, which is impacted by body size and UF volume. A Dt/V of >1.2 strongly predicts adequate dialysis as defined by Kt/V of >1.2.

Interactions between the sympathetic nervous system and angiotensin system in renovascular hypertension.

Renal artery stenosis especially that due to atherosclerotic peripheral vascular disease is increasing in the population. The role of the renin angiotensin aldosterone system in the pathogenesis of renovascular hypertension is widely accepted. There is increasing recognition of the role of the sympathetic nervous system, from both afferent and efferent signaling pathways, as a contributor to development of hypertension. In this review we briefly summarize the experimental evidence for the respective roles of the renin angiotensin aldosterone system and the sympathetic nervous system as well as their interaction in renovascular hypertension.