Background Dietary potassium (K+) has emerged as a modifiable factor for cardiovascular and kidney health in the general population, but its role in people with chronic kidney disease (CKD) is... Show moreBackground Dietary potassium (K+) has emerged as a modifiable factor for cardiovascular and kidney health in the general population, but its role in people with chronic kidney disease (CKD) is unclear. Here, we hypothesize that CKD increases the susceptibility to the negative effects of low and high K+ diets.Methods We compared the effects of low, normal and high KChloride (KCl) diets and a high KCitrate diet for 4 weeks in male rats with normal kidney function and in male rats with CKD using the 5/6th nephrectomy model (5/6Nx).Results Compared with rats with normal kidney function, 5/6Nx rats on the low KCl diet developed more severe extracellular and intracellular K+ depletion and more severe kidney injury, characterized by nephromegaly, infiltration of T cells and macrophages, decreased estimated glomerular filtration rate and increased albuminuria. The high KCl diet caused hyperkalemia, hyperaldosteronism, hyperchloremic metabolic acidosis and severe hypertension in 5/6Nx but not in sham rats. The high KCitrate diet caused hypochloremic metabolic alkalosis but attenuated hypertension despite higher abundance of the phosphorylated sodium chloride cotransporter (pNCC) and similar levels of plasma aldosterone and epithelial sodium channel abundance. All 5/6Nx groups had more collagen deposition than the sham groups and this effect was most pronounced in the high KCitrate group. Plasma aldosterone correlated strongly with kidney collagen deposition.Conclusions CKD increases the susceptibility to negative effects of low and high K+ diets in male rats, although the injury patterns are different. The low K+ diet caused inflammation, nephromegaly and kidney function decline, whereas the high K+ diet caused hypertension, hyperaldosteronism and kidney fibrosis. High KCitrate attenuated the hypertensive but not the pro-fibrotic effect of high KCl, which may be attributable to K+-induced aldosterone secretion. Our data suggest that especially in people with CKD it is important to identify the optimal threshold of dietary K+ intake.Graphical Abstract Show less
Rationale & Objective: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between... Show moreRationale & Objective: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5.Study Design: Prospective observational cohort study.Setting & Participants: We followed 1,714 patients (>= 65 years old) from the European Quality (EQUAL) study for 8 years from their first estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m(2) measurement. Exposure: Serum potassium was measured every 3 to 6 months and categorized as <= 3.5, >3.5-<= 4.0, >4.0-<= 4.5, >4.5-<= 5.0 (reference), >5.0-<= 5.5, >5.5-<= 6.0, and >6.0 mmol/L.Outcome: The combined outcome death before KRT or start of KRT.Analytical Approach: The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, renin-angiotensin-aldosterone system (RAAS) inhibition, eGFR, and subjective global assessment (SGA).Results: At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease, and 54% used RAAS inhibitors. Their mean age was 76 +/- 7 (SD) years, mean eGFR was 17 +/- 5 (SD) mL/min/1.73 m(2), and mean SGA was 6.0 +/- 1.0 (SD). Over 8 years, 414 (24%) died before starting KRT, and 595 (35%) started KRT. Adjusted hazard ratios for death or KRT according to the potassium categories were 1.6 (95% CI, 1.1-2.3), 1.4 (95% CI, 1.1-1.7), 1.1 (95% CI, 1.0-1.4), 1 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.5-3.3). Hazard ratios were lowest at a potassium of about 4.9 mmol/L.Limitations: Shorter intervals between potassium measurements would have allowed for more precise estimations.Conclusions: We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD 4- 5, with a nadir risk at a potassium level of 4.9 mmol/L. These findings underscore the potential importance of preventing both high and low potassium in patients with CKD 4-5. Show less
Wouda, R.D.; Gritter, M.; Karsten, M.; Michels, E.H.A.; Nieuweboer, T.M.; Danser, A.H.J.; ... ; Vogt, L. 2023
Background A potassium replete diet is associated with lower cardiovascular risk but may increase the risk of hyperkalemia, particularly in people using renin-angiotensin-aldosterone system... Show moreBackground A potassium replete diet is associated with lower cardiovascular risk but may increase the risk of hyperkalemia, particularly in people using renin-angiotensin-aldosterone system inhibitors. We investigated whether intracellular uptake and potassium excretion after an acute oral potassium load depend on the accompanying anion and/or aldosterone and whether this results in altered plasma potassium change.Methods In this placebo-controlled interventional cross-over trial including 18 healthy individuals, we studied the acute effects of one oral load of potassium citrate (40 mmol), potassium chloride (40 mmol), and placebo in random order after overnight fasting. Supplements were administered after a 6-week period with and without lisinopril pretreatment. Linear mixed effect models were used to compare blood and urine values before and after supplementation and between the interventions. Univariable linear regression was used to determine the association between baseline variables and change in blood and urine values after supplementation.Results During the 4-hour follow-up, the rise in plasma potassium was similar for all interventions. After potassium citrate, both red blood cell potassium-as measure of the intracellular potassium-and transtubular potassium gradient (TTKG)-reflecting potassium secretory capacity-were higher than after potassium chloride or potassium citrate with lisinopril pretreatment. Baseline aldosterone was significantly associated with TTKG after potassium citrate, but not after potassium chloride or potassium citrate with lisinopril pretreatment. The observed TTKG change after potassium citrate was significantly associated with urine pH change during this intervention (R50.60, P, 0.001).Conclusions With similar plasma potassium increase, red blood cell potassium uptake and kaliuresis were higher after an acute load of potassium citrate as compared with potassium chloride alone or pretreatment with lisinopril. Show less
Background: Low 24-h urinary potassium excretion, reflecting low potassium intake, is associated with premature mortality in the general population. Objectives: To determine whether urinary... Show moreBackground: Low 24-h urinary potassium excretion, reflecting low potassium intake, is associated with premature mortality in the general population. Objectives: To determine whether urinary potassium excretion is associated with all-cause mortality in patients with type 2 diabetes. Methods: We performed a prospective cohort study in 654 patients with type 2 diabetes in the Diabetes and Lifestyle Cohort Twente (DIALECT). Sex-specific tertiles of 24-h urinary potassium excretion were analyzed in a multivariable Cox regression model with all-cause mortality. The outpatient program of the hospital uses a continuous surveillance system by the municipal registry of death to ensure up-to-date information on the patient's status (alive or deceased). FFQs were used to study associations between urinary potassium excretion and food products. Results: Urinary potassium excretion at baseline was 84 & PLUSMN; 25 mmol/d in males and 65 & PLUSMN; 22 mmol/d in females, corresponding to estimated potassium intakes of 4250 & PLUSMN; 1270 mg/d and 3300 & PLUSMN; 875 mg/d. During a median follow-up of 5.2 (IQR: 2.7-7.9] y, 96 participants died. In a fully adjusted model, patients in the lowest sex-specific tertile had a higher risk of all-cause mortality, compared with patients in the highest sex-specific tertile (HR: 2.09; 95% CI: 1.06, 4.10; P = 0.03). Patients in the lowest sex-specific tertile consumed fewer fruits and vegetables, dairy, coffee, and potato products compared with patients in the highest sex-specific tertile (all P < 0.05). Conclusions: Low potassium intake is associated with a higher risk of all-cause mortality in Dutch patients with type 2 diabetes. Intervention studies are needed to determine whether potassium supplementation improves longevity in patients with type 2 diabetes. This trial was registered in the as NTR trial code 5855. Show less
Aims A potassium replete diet is associated with lower blood pressure (BP) and lower risk of cardiovascular disease (CVD). Whether these associations differ between men and women and whether they... Show moreAims A potassium replete diet is associated with lower blood pressure (BP) and lower risk of cardiovascular disease (CVD). Whether these associations differ between men and women and whether they depend on daily sodium intake is unknown. Methods and results An analysis was performed in 11 267 men and 13 696 women from the EPIC-Norfolk cohort. Twenty-four hour excretion of sodium and potassium, reflecting intake, was estimated from sodium and potassium concentration in spot urine samples using the Kawasaki formula. Linear and Cox regression were used to explore the association between potassium intake, systolic BP (SBP), and CVD events (defined as hospitalization or death due to CVD). After adjustment for confounders, interaction by sex was found for the association between potassium intake and SBP (P < 0.001). In women, but not in men, the inverse slope between potassium intake and SBP was steeper in those within the highest tertile of sodium intake compared with those within the lowest tertile of sodium intake (P < 0.001 for interaction by sodium intake). Both in men and women, higher potassium intake was associated with a lower risk of CVD events, but the hazard ratio (HR) associated with higher potassium intake was lower in women than in men [highest vs. lowest potassium intake tertile: men: HR 0.93, 95% confidence interval (CI) 0.87-1.00; women: HR 0.89, 95% CI 0.83-0.95, P = 0.033 for interaction by sex]. Conclusion The association between potassium intake, SBP, and CVD events is sex specific. The data suggest that women with a high sodium intake in particular benefit most from a higher potassium intake with regard to SBP. Show less
Background Potassium intake has been shown to be inversely associated with blood pressure and premature mortality. Previous studies have suggested that the association between potassium intake and... Show moreBackground Potassium intake has been shown to be inversely associated with blood pressure and premature mortality. Previous studies have suggested that the association between potassium intake and blood pressure is modified by obesity, but whether obesity similarly influences the association between potassium intake and mortality is unclear. Objectives We investigated whether potassium intake, reflected by 24-h urinary excretion, is associated with all-cause mortality, and explored potential effect modification by obesity. Methods We performed a prospective cohort study in community-dwelling individuals. The association between urinary potassium excretion and all-cause mortality was investigated by using multivariable Cox regression. We performed multiplicative interaction analysis and subgroup analyses according to BMI and waist circumference. Results In 8533 individuals (50% male), the mean age was 50 +/- 13 y, mean urinary potassium excretion was 71 +/- 21 mmol/24 h, median BMI (in kg/m(2)) was 25.6 (IQR: 23.1, 28.4) and mean waist circumference was 89 +/- 13 cm. During median follow-up of 18.4 (IQR: 13.5, 18.8) y, 1663 participants died. Low urinary potassium excretion (first compared with third sex-specific quintile) was associated with an increased mortality risk (fully adjusted HR: 1.38; 95% CI: 1.18, 1.61), P < 0.001, irrespective of body dimensions (HR range for all body dimensions: 1.36-1.70, all P < 0.05). High urinary potassium excretion (fifth compared with third quintile) was associated with increased mortality risk in participants with obesity (BMI >= 30; HR: 1.52; CI: 1.00, 2.30), but not in participants without obesity (BMI: <25; HR: 0.89; 95% CI: 0.62, 1.26; P-interaction = 0.001). Conclusions Low potassium intake was associated with increased mortality risk in community-dwelling individuals. In individuals with obesity, high potassium intake was also associated with increased mortality risk. Show less
By controlling urinary potassium excretion, the kidneys play a key role in maintaining whole-body potassium homeostasis. Conversely, low urinary potassium excretion (as a proxy for insufficient... Show moreBy controlling urinary potassium excretion, the kidneys play a key role in maintaining whole-body potassium homeostasis. Conversely, low urinary potassium excretion (as a proxy for insufficient dietary intake) is increasingly recognized as a risk factor for the progression of kidney disease. Thus, there is a reciprocal relationship between potassium and the kidney: the kidney regulates potassium balance but potassium also affects kidney function. This review explores this relationship by discussing new insights into kidney potassium handling derived from recently characterized tubulopathies and studies on sexual dimorphism. These insights reveal a central but non-exclusive role for the distal convoluted tubule in sensing potassium and subsequently modifying the activity of the sodium-chloride cotransporter. This is another example of reciprocity: activation of the sodium-chloride cotransporter not only reduces distal sodium delivery and therefore potassium secretion but also increases salt sensitivity. This mechanism helps explain the well-known relationship between dietary potassium and blood pressure. Remarkably, in children, blood pressure is related to dietary potassium but not sodium intake. To explore how potassium deficiency can cause kidney injury, we review the mechanisms of hypokalemic nephropathy and discuss if these mechanisms may explain the association between low dietary potassium intake and adverse kidney outcomes. We discuss if potassium should be repleted in patients with kidney disease and what role dietary potassium plays in the risk of hyperkalemia. Supported by data and physiology, we reach the conclusion that we should view potassium not only as a potentially dangerous cation but also as a companion in the battle against kidney disease. Show less
Rooij, E.N.M. de; Dekker, F.W.; Cessie, S. le; Hoorn, E.J.; Fijter, J.W. de; Hoogeveen, E.K.; Netherlands Cooperative Study Adeq 2022
Rationale & Objective: Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients... Show moreRationale & Objective: Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients receiving hemodialysis, especially for hypokalemia, this risk may be underestimated. Therefore, we investigated the relationship between predialysis serum potassium level and death in incident hemodialysis patients and whether there is an optimum level.Study Design: Prospective multicenter cohort study.Setting & Participants: 1,117 incident hemodialysis patients (aged >18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 study were included and followed from their first hemodialysis treatment until death, transplantation, switch to peritoneal dialysis, or a maximum of 10 years.Exposure: Predialysis serum potassium levels were obtained every 6 months and divided into 6 categories: =4.0 mmol/L, >4.0 mmol/L to =4.5 mmol/ L, >4.5 mmol/ L to =5.0 mmol/L, >5.0 mmol/ L to =5.5 mmol/L (reference), >5.5 mmol/L to =6.0 mmol/ L, and >6.0 mmol/L. Outcomes: 6-month all-cause mortality.Analytical Approach: Cox proportional hazards and restricted cubic spline analyses with time-dependent predialysis serum potassium levels were used to calculate the adjusted HRs for death.Results: At baseline, the mean age of the patients was 63 years (standard deviation, 14 years), 58% were men, 26% smoked, 24% had diabetes, 32% had cardiovascular disease, the mean serum potassium level was 5.0 mmol/L (standard deviation, 0.8 mmol/L), 7% had a low subjective global assessment score, and the median residual kidney function was 3.5 mL/min/1.73 m2 (IQR, 1.4-4.8 mL/min/1.73 m2). During the 10-year follow-up, 555 (50%) deaths were observed. Multivariable adjusted HRs for death according to the 6 potassium categories were as follows: 1.42 (95% CI, 1.01-1.99), 1.09 (95% CI, 0.82-1.45), 1.21 (95% CI, 0.94-1.56), 1 (reference), 0.95 (95% CI, 0.71-1.28), and 1.32 (95% CI, 0.97-1.81). Limitations: Shorter intervals between potassium measurements would have allowed for more precise mortality risk estimations.Conclusions: We found a U-shaped relationship between serum potassium level and death in incident hemodialysis patients. A low predialysis serum potassium level was associated with a 1.4-fold stronger risk of death than the optimal level of approximately 5.1 mmol/L. These results may imply the cautious use of potassium-lowering therapy and a potassium-restricted diet in patients receiving hemodialysis. Show less
High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23... Show moreHigh plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2-77.8) RU/mL in men, and 70.3 (56.5-89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. beta -0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01-1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01-1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population. Show less
Background. Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown.Methods. Patients... Show moreBackground. Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown.Methods. Patients with ADPKD from the D1PAK (Developing Interventions to halt Progression of ADPKD) trial were included [n= 296, estimated glomerular filtration rate (eGFR) 50 +/- 11 mL/min/1.73 m(2), 25 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid-base parameters (urinary ammonium excretion).Results. Patients in the lowest tertile of baseline serum bicarbonate (23.1 +/- 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21-7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 +/- 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06-1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (-0.12 mL/min/1.73 m(2)/year, 95% CI -0.20 to -0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth.Conclusions. In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD. Show less
Koh, E.Y.; Plas, W.Y. van der; Dulfer, R.R.; Pol, R.A.; Kruijff, S.; Rotmans, J.I.; ... ; Dutch Hyperparathyroidism Study 2021
Background Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate... Show moreBackground Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis.Methods Patients with CKD stage G4 and plasma bicarbonate 15-24 mmol/l were randomized to receive sodium bicarbonate (3 x 1000 mg/day, similar to 0.5 mEq/kg), sodium chloride (2 x 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed.Results Forty-five patients were included (62 +/- 15 years, eGFR 21 +/- 5 ml/min/1.73m(2), plasma bicarbonate 21.7 +/- 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or alpha 1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and alpha 1-microglobulin (all P < 0.05).Conclusions Despite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity. Show less
Potassiumoften has a negative connotation in Nephrology as patients with chronic kidney disease (CKD) are prone to develop hyperkalaemia. Approaches to the management of chronic hyperkalaemia... Show morePotassiumoften has a negative connotation in Nephrology as patients with chronic kidney disease (CKD) are prone to develop hyperkalaemia. Approaches to the management of chronic hyperkalaemia include a low potassium diet or potassiumbinders. Yet, emerging data indicate that dietary potassium may be beneficial for patients with CKD. Epidemiological studies have shown that a higher urinary potassium excretion (as proxy for higher dietary potassium intake) is associated with lower blood pressure (BP) and lower cardiovascular risk, as well as better kidney outcomes. Considering that the composition of our current diet is characterized by a high sodium and low potassium content, increasing dietary potassium may be equally important as reducing sodium. Recent studies have revealed that dietary potassiummodulates the activity of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule (DCT). The DCT acts as a potassium sensor to control the delivery of sodium to the collecting duct, the potassium-secreting portion of the kidney. Physiologically, this allows immediate kaliuresis after a potassium load, and conservation of potassiumduring potassium deficiency. Clinically, it provides a novel explanation for the inverse relationship between dietary potassium and BP. Moreover, increasing dietary potassium intake can exert BP-independent effects on the kidney by relieving the deleterious effects of a low potassium diet (inflammation, oxidative stress and fibrosis). The aim of this comprehensive review is to link physiology with clinical medicine by proposing that the same mechanisms that allow us to excrete an acute potassiumload also protect us from hypertension, cardiovascular disease and CKD. Show less
Context: Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 ... Show moreContext: Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23), are unclear.Objective: Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters.Design, setting, participants: We performed a post hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Prehypertensive individuals not using antihypertensive medication (n = 36) received capsules containing potassium chloride (3 g/d), sodium chloride (3 g/d), or placebo. Linear mixed-effect models were used to estimate treatment effects.Results: Potassium supplementation increased plasma phosphate (from 1.10 +/- 0.19 to 1.15 +/- 0.19 mmol/L, P = 0.004), in line with an increase in tubular maximum of phosphate reabsorption (from 0.93 +/- 0.21 to 1.01 +/- 0.20 mmol/L, P < 0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, P = 0.01), without change in parathyroid hormone and 25-hydroxy vitamin D 3. Fractional calcium excretion decreased (from 1.25 +/- 0.50 to 1.11 +/- 0.46 %, P = 0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10 +/- 0.19 to 1.06 +/- 0.21 mmol/L, P = 0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P = 0.02). Urinary and fractional calcium excretion increased (from 4.28 +/- 1.91 to 5.45 +/- 2.51 mmol/24 hours, P < 0.001, and from 1.25 +/- 0.50 to 1.44 +/- 0.54 %, P = 0.004, respectively).Conclusions: Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23. Show less
Koh, E.Y.; Plas, W.Y. van der; Dulfer, R.R.; Pol, R.A.; Kruijf, S.; Rotmans, J.I.; ... ; Dutch Hyperparathyroidism Study Gr 2020
Purpose Calcimimetics are currently indicated for severe secondary hyperparathyroidism (SHPT). However, the role of parathyroidectomy (PTX) for these patients is still under debate, and its impact... Show morePurpose Calcimimetics are currently indicated for severe secondary hyperparathyroidism (SHPT). However, the role of parathyroidectomy (PTX) for these patients is still under debate, and its impact on subsequent kidney transplantation (KTX) is unclear. In this study, we compare the outcomes of kidney transplantation after PTX or medical treatment. Methods Patients who underwent KTX and had SHPT were analyzed retrospectively. Two groups were selected (patients who had either PTX or calcimimetics prior to KTX) using a propensity score for sex, age, donor type, and parathyroid hormone levels (PTH) during dialysis. The primary outcome was graft failure, and secondary outcomes were surgical KTX complications, survival, serum PTH, serum calcium, and serum phosphate levels post-KTX. Results Matching succeeded for 92 patients. After PTX, PTH was significantly lower on the day of KTX as well as at 1 and 3 years post-KTX (14.00 pmol/L (3.80-34.00) vs. 71.30 pmol/L (30.70-108.30),p < 0.01, 10.10 pmol/L (2.00-21.00) vs. 32.35 pmol/L (21.58-51.76),p < 0.01 and 13.00 pmol/L (6.00-16.60) vs. 19.25 pmol/L (13.03-31.88),p = 0.027, respectively). No significant differences in post-KTX calcium and phosphate levels were noted between groups. Severe KTX complications were more common in the calcimimetics group (56.5% vs. 30.4%,p = 0.047). There were no differences in 10-year graft failure and overall survival. Conclusion PTX resulted in lower PTH after KTX in comparison to patients who received calcimimetics. Severe complications were more common after calcimimetics, but graft failure and overall survival were similar. Show less
Janki, S.; Dehghan, A.; Wetering, J. van de; Steyerberg, E.W.; Klop, K.W.J.; Kimenai, H.J.A.N.; ... ; Ijzermans, J.N.M. 2020
Background Live donor nephrectomy is a safe procedure. However, long-term donor prognosis is debated, necessitating high-quality studies. Methods A follow-up study of 761 living kidney donors was... Show moreBackground Live donor nephrectomy is a safe procedure. However, long-term donor prognosis is debated, necessitating high-quality studies. Methods A follow-up study of 761 living kidney donors was conducted, who visited the outpatient clinic and were propensity score matched and compared to 1522 non-donors from population-based cohort studies. Primary outcome was kidney function. Secondary outcomes were BMI (kg/m(2)), incidences of hypertension, diabetes, cardiovascular events, cardiovascular and overall mortality, and quality of life. Results Median follow-up after donation was 8.0 years. Donors had an increase in serum creatinine of 26 mu mol/l (95% CI 24-28), a decrease in eGFR of 27 ml/min/1.73 m(2) (95% CI - 29 to - 26), and an eGFR decline of 32% (95% CI 30-33) as compared to non-donors. There was no difference in outcomes between the groups for ESRD, microalbuminuria, BMI, incidence of diabetes or cardiovascular events, and mortality. A lower risk of new-onset hypertension (OR 0.45, 95% CI 0.33-0.62) was found among donors. The EQ-5D health-related scores were higher among donors, whereas the SF-12 physical and mental component scores were lower. Conclusion Loss of kidney mass after live donation does not translate into negative long-term outcomes in terms of morbidity and mortality compared to non-donors. Show less
Kenter, A.T.; Rentmeester, E.; Riet, J. van; Boers, R.; Boers, J.; Ghazvini, M.; ... ; Gribnau, J.H. 2020
Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure in most patients. In approximately 85% of cases, the disease is caused by... Show moreAutosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure in most patients. In approximately 85% of cases, the disease is caused by mutations in PKD1. How dysregulation of PKD1 leads to cyst formation on a molecular level is unknown. Induced pluripotent stem cells (iPSCs) are a powerful tool for in vitro modeling of genetic disorders. Here, we established ADPKD patient-specific iPSCs to study the function of PKD1 in kidney development and cyst formation in vitro. Somatic mutations are proposed to be the initiating event of cyst formation, and therefore, iPSCs were derived from cystic renal epithelial cells rather than fibroblasts. Mutation analysis of the ADPKD iPSCs revealed germline mutations in PKD1 but no additional somatic mutations in PKD1/PKD2. Although several somatic mutations in other genes implicated in ADPKD were identified in cystic renal epithelial cells, only few of these mutations were present in iPSCs, indicating a heterogeneous mutational landscape, and possibly in vitro cell selection before and during the reprogramming process. Whole-genome DNA methylation analysis indicated that iPSCs derived from renal epithelial cells maintain a kidney-specific DNA methylation memory. In addition, comparison of PKD1+/- and control iPSCs revealed differences in DNA methylation associated with the disease history. In conclusion, we generated and characterized iPSCs derived from cystic and healthy control renal epithelial cells, which can be used for in vitro modeling of kidney development in general and cystogenesis in particular. Show less
Plas, W.Y. van der; Moumni, M. el; Forstner, P.J. von; Koh, E.Y.; Dulfer, R.R.; Ginhoven, T.M. van; ... ; Dutch Hyperparathyroidism Study Gr 2019
BackgroundParathyroidectomy (PTx) is the treatment of choice for end-stage renal disease (ESRD) patients with therapy-resistant hyperparathyroidism (HPT). The optimal timing of PTx for ESRD-related... Show moreBackgroundParathyroidectomy (PTx) is the treatment of choice for end-stage renal disease (ESRD) patients with therapy-resistant hyperparathyroidism (HPT). The optimal timing of PTx for ESRD-related HPTbefore or after kidney transplantation (KTx)is subject of debate.MethodsPatients with ESRD-related HPT who underwent both PTx and KTx between 1994 and 2015 were included in a multicenter retrospective study in four university hospitals. Two groups were formed according to treatment sequence: PTx before KTx (PTxKTx) and PTx after KTx (KTxPTx). Primary endpoint was renal function (eGFR, CKD-EPI) between both groups at several time points post-transplantation. Correlation between the timing of PTx and KTx and the course of eGFR was assessed using generalized estimating equations (GEE).ResultsThe PTxKTx group consisted of 102 (55.1%) and the KTxPTx group of 83 (44.9%) patients. Recipient age, donor type, PTx type, and pre-KTx PTH levels were significantly different between groups. At 5years after transplantation, eGFR was similar in the PTxKTx group (eGFR 44.54.0ml/min/1.73m(2)) and KTxPTx group (40.0 +/- 6.4ml/min/1.73m(2), p=0.43). The unadjusted GEE model showed that timing of PTx was not correlated with graft function over time (mean difference -1.0ml/min/1.73m(2), 95% confidence interval -8.4 to 6.4, p=0.79). Adjustment for potential confounders including recipient age and sex, various donor characteristics, PTx type, and PTH levels did not materially influence the results.Conclusions In this multicenter cohort study, timing of PTx before or after KTx does not independently impact graft function over time. Show less
Oevelen, M. van; Abrahams, A.C.; Weijmer, M.C.; Nagtegaal, T.; Dekker, F.W.; Rotmans, J.I.; ... ; DUCATHO Study Grp 2019
