Association of Urinary Potassium Excretion with Blood Pressure Variability and Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease

Dietary potassium intake is a dilemma in patients with chronic kidney disease (CKD). We investigated the association of urine potassium excretion, a surrogate for dietary potassium intake, with blood pressure variability (BPV) and cardiovascular (CV) outcomes in patients with pre-dialysis CKD. A total of 1860 participants from a cohort of pre-dialysis CKD (KNOW-CKD) patients were divided into the quartiles by spot urine potassium-to-creatinine ratio. The first quartile (26.423 ± 5.731 mmol/gCr) was defined as low urine potassium excretion. Multivariate linear regression analyses revealed an independent association of low urine potassium excretion with high BPV (adjusted β coefficient 1.163, 95% confidence interval 0.424 to 1.901). Cox regression analyses demonstrated that, compared to high urine potassium excretion, low urine potassium excretion is associated with increased risk of CV events (adjusted hazard ratio 2.502, 95% confidence interval 1.162 to 5.387) but not with all-cause mortality. In conclusion, low urine potassium excretion is associated with high BPV and increased risk of CV events in patients with pre-dialysis CKD. The restriction of dietary potassium intake should be individualized in patients with pre-dialysis CKD.

MO053GITELMAN'S SYNDROME AND PREGNANCY: TWO SUCCESSFUL CASE REPORTS

Background and Aims Gitelman’s Syndrome (GS) is a rare autosomal recessive hereditary salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. Pregnancy in women with GS often aggravates hypokalemia and hypomagnesemia. However, there are few reports of pregnancies in GS. Here, we report the course of two Chinese women who were diagnosed as GS during pregnancy in 2019 and 2020 respectively. Method Case 1: A 21-year-old woman was referred to our hospital at 9 weeks gestation of her first pregnancy. She had complained of muscle weakness and cramps for one year. Before the referral she was diagnosed as hypokalemia and treated by oral potassium supplementation. However, her symptoms became severer after pregnancy. Case 2: A 20-year-old woman was admitted to the hospital because of elevated plasma glucose level and hypokalemia at 27 weeks gestation of her first pregnancy. The woman was asymptomatic and denied history of chronic diseases. The laboratory examinations were taken after admission. Genetic testing was conducted for pathogenic mutations in SLC12A3 (GS) and SLC12A1, KCNJ1, CLCKNB and BSND (Bartter syndrome 1-4). Results Case 1: Initial biochemistry examinations revealed hypokalemia (2.3 mmol/L, normal range 3.5-5.3 mmol/L) with inappropriate renal potassium wasting (urine potassium 254 mmol/24h, normal range < 20 mmol/24h), alkalosis (arterial blood gas pH 7.49), hypomagnesemia (0.55 mmol/L, normal range 0.67-1.04 mmol/L), hypocalciuria (urine calcium 1.6 mmol/24h, normal range 2.5-7.5 mmol/24h) and elevated renin (276 pg/ml, normal range 4-24 pg/ml) and aldosterone (825 pg/ml, normal range 10-160 pg/ml) levels. The blood pressure was normal-low (97/68 mmHg, 12.9/9.0 kPa) and the renal ultrasound was normal. Homozygous mutations [c.179C>T (Thr60Met)] were identified. The woman’s father and sister had a heterozygous c.179C>T, but had no electrolyte disorders. After the treatment of oral potassium supplementation (KCl 3g tid) and spironolactone (40mg bid), her serum potassium level increased to 3.4-4.0 mmol/L and muscle weakness was relieved. The woman delivered a healthy female infant weighing 2600 g at 39 weeks gestation via cesarean section. Maternal serum potassium level remained normal and no symptoms reoccured after delivery. Case 2: Initial biochemistry examinations identified hypokalemia (2.3 mmol/L, normal range 3.5-5.3 mmol/L) with inappropriate renal potassium wasting (urine potassium 81 mmol/24h, normal range < 20 mmol/24h), hypomagnesemia (0.49 mmol/L, normal range 0.67-1.04 mmol/L), hypocalciuria (urine calcium 0.3 mmol/24h, normal range 2.5-7.5 mmol/24h) and elevated renin (54 pg/ml, normal range 4-24 pg/ml) and aldosterone (834 pg/ml, normal range 10-160 pg/ml) levels. The blood pressure and renal ultrasound were normal. Heterozygous mutations [c.179C>T (Thr60Met), c.658G>A (Gly220Ser)] were identified. The woman was treated by oral potassium supplementation (KCl 3g tid) and her serum potassium level maintained normal during pregnancy. She had a normal delivery of a healthy female infant weighing 3050 g at 40 weeks gestation. After delivery she discontinued oral potassium supplementation and her serum potassium level ranged from 3.0-3.4 mmol/L without symptoms. Conclusion The outcome of mother and fetus of GS pregnancies appears favorable. Intensive monitoring of electrolyte levels and sufficient electrolyte supplementation are advised during pregnancy.

Potassium Electrolyte Serum - Urine , and Creatinine in Chronic Kidney Diseases

Background: The kidneys are important organs in the human body that have many functions. Kidney function is divided into several processes, namely filtration, reabsorption and secretion of substances in the body. Nephron which is the smallest kidney functional unit that is responsible for accommodating all functions in the kidney. One of the functions of the kidneys is secretion, the secretions in the kidneys work by removing electrolytes and other substances that are no longer needed by the body through urine. When the function of the kidney nephrons is disturbed, it can result in an electrolyte imbalance (K), a buildup of waste from substances that are not needed by the body (creatinine). The objective of this research was to examine the relationship between electrolytes (K) serum, urine and creatinine in patients with CKD.Methods: The research was conducted by observational, anamnesis, and sampling of CKD patients at Dr. Kariadi Semarang during the period March-May 2020.Results: The results of the multivariate linear regression test showed that creatinine had a moderate significant positive effect at p = 0.024 and r = 0.412 on serum K. Meanwhile, from multivariate linear regression, it was found that creatinine had a moderate negative effect at p = 0.027 and r = -0.456 on urine K.Conclusions and suggestions: The findings proved the relationship between creatinine levels and serum and urine potassium levels in patients with CKD. Serum and urine electrolytes can be used as an parameter for CKD management.

A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout

The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: −0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by −0.48 mg/dL (95% CI: −0.98, 0.01) compared to DDG by −0.05 mg/dL (95% CI: −0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: −34.0, −8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.

Aldosterone sensitivity: an opportunity for investigation into the pathogenesis of hypertension

Aldosterone sensitivity is defined as an outcome variable for a given circulating level of aldosterone. In basic and translational studies, this has been measured in differential tissue responses, e.g. lower urine sodium and higher urine potassium, as an index of renal response; and in clinical studies has been measured in differential blood pressure. This concept of aldosterone sensitivity disrupts the conventional wisdom of the renin-angiotensin-aldosterone system and has the potential to uncover novel mechanisms of hypertension. We review basic and translational science studies that uncovered differential renal responses to aldosterone and connect this earlier work to more recent observational and randomized trials that have demonstrated differential blood pressure for a given level of aldosterone in healthy and hypertensive subjects. Black race and age are associated with higher aldosterone sensitivity and blood pressure. We also discuss gaps in the field and how future basic and clinical studies can inform mechanisms of differential sensitivity.

A Case Report of Recurrent Hypokalemia During Pregnancies Associated With Nonaldosterone-Mediated Renal Potassium Loss

Rationale: Geller et al reported a rare mutation in the mineralocorticoid receptor (MR) resulting in constitutive MR activity. Progesterone, normally an MR antagonist, acts as a potent agonist with this mutation. Progesterone levels can increase 100-fold during pregnancy and thus lead to increased MR activity in this setting, resulting in hypertension (HTN) and hypokalemia during pregnancy and resolution of hypokalemia after delivery. Presenting concerns: Our patient was a 33-year-old African American female with a history of pregnancy-induced HTN associated with hypokalemia during her last pregnancy. She presented with muscle weakness from profound hypokalemia complicated by nephrogenic diabetes insipidus (DI) and rhabdomyolysis. Diagnosis: Her admission potassium was 1.9 mmol/L (3.5-5.1 mmol/L) with a 24-hour urine potassium of 35 mmol per day and an unmeasurable serum aldosterone level. Her potassium normalized 1 day after delivery off potassium supplementation and amiloride, which were last given 1 day prior to her delivery. Recurrent hypokalemia from nonaldosterone-mediated renal potassium wasting during pregnancy (with normal potassium in a nongestational state) is consistent with the cases of gain-of-function mutation in MR that Geller et al report. A definite diagnosis requires genetic analysis. Interventions: Her hypokalemia was refractory to potassium replacement but quickly responded to an inhibitor of the epithelial sodium channel (ENaC), amiloride. Outcomes: Her potassium normalized on amiloride 10 mg per day and KCL 40 mEq daily during the remainder of her pregnancy, and her nephrogenic DI resolved after this correction of hypokalemia. After her delivery, her potassium remained normal off the potassium supplements and amiloride. Novel findings: Pregnancy-induced hypokalemia from an activating MR mutation has rarely been reported. Pregnancy-induced HTN is often the first differential diagnosis in a patient who develops worsening in her HTN during pregnancy. We should also consider the possibility of a gain-of-function mutation in MR in these patients who also have associated hypokalemia.

Genetic Analysis of Gitelman Syndrome Co-Existent with Hyperthyroidism in a 2 Years Old Boy

: A two-year-old boy went to the doctor for hypokalemia and metabolic alkalosis. Laboratory examination revealed that urinary potassium excretion and serum aldosterone level increased, at the same time with hyperthyroidism and thyroid related antibodies positive.Genetic testing showed that there was a complex heterozygous mutation in SLC12A3 gene ,c.1077C>G(p.N359K) and c.1567G>A(p.A523?)，the final diagnosis was Gitelman syndrome and autoimmune hyperthyroidism.Gitelman syndrome is an autosomal recessive genetic disease caused by the inactivation mutation of SLC12A3 gene. The onset age is more than 6 years old, mainly manifested as low blood potassium, low blood sodium, low blood chlorine, metabolic alkalosis, increased urine potassium and urine chlorine excretion and low urine calcium.Autoimmune hyperthyroidism due to the autoimmune disorders. The highest incidence rate in children is Graves' disease, followed by chronic lymphocytic thyroiditis.Several cases of Gitelman syndrome with autoimmune hyperthyroidism had been identified, most of which were Asian adults, and the case we identified is the first reported case of children under 14 years old with both Gitelman syndrome and autoimmune hyperthyroidism.At the same time, we carried out high-precision clinical exosome analysis of the gene of this case, and further explored the relationship between Gitelman syndrome and autoimmune hyperthyroidism from the perspective of gene.

Urinary excretion of electrolytes and their correlation with clinical parameters in chronic kidney disease

Introduction: With the increasing incidence of chronic renal disease on a global scale, it is important to document the chemical abnormalities that not only indicate deteriorating renal function, but also aggravate the clinical picture by causing sustained electrolyte imbalance, ultimately contributing to End Stage Renal Disease (ESRD). Objective: To investigate 24-hr urinary electrolytes excretion of non-dialysis patients presenting with history of chronic kidney disease (CKD) and correlate the biochemical abnormalities with clinical parameters. Materials & Methods: A total of 100 patients with CKD were included in a private clinic setup from February 2017 to December 2019 to retrospectively analyze the relationship of 24-hr urinary electrolytes with clinical indicators in these subjects. Besides demographic data, biochemical indices of concern were obtained through standard laboratory techniques. The patients were then divided on the basis of results into four quartile groups. Descriptive data analysis was done through SPSS 22.0. Results: Nephropathic patients had low eGFR, albumin, hemoglobin, blood calcium as well as 24-hr urine calcium and had high body mass index (BMI), systolic blood pressure, diastolic blood pressure, blood creatinine, blood sodium and 24-hr urine sodium. According to quartiles of 24-hr urinary sodium; in the Q4 group, 24-hr urine protein, 24-hr urine potassium and 24-hr urine calcium were the highest while according to quartile of 24-hr urinary potassium; the Q3 group had the highest 24-hr urine protein. According to quartile of urinary calcium, Q4 group blood calcium, 24-hr urine sodium and 24-hr urine potassium was high. The results revealed a positive correlation of 24-hr urinary sodium and potassium with 24-hr urine protein and a negative correlation of 24⁃hr urinary calcium with 24-hr urine protein. Conclusion: The levels of urinary electrolytes in patients with CKD are associated with urinary protein. It is, therefore, recommended that the above-mentioned disease be treated in these patients for their proper management. Keywords: Urine Chemistry; Proteinuria; Renal Insufficiency, Chronic.

Changes in Renal Parameters during a Training Camp among Handball Players in the Sub-Saharan Environment

The aim of the study was to describe the changes in kidney parameters induced by 10 days of tapering (TP) during a training camp (TC), where the players were preparing for a group competition, in 15 female handball team members of a Division 1 Amateur of Benin, in the sub-Saharan environment. Measures were taken in all the players before and after the intensive training (IT) and tapering (TP) phases in an intervention study. The estimated glomerular filtration rate (eGFR) with the CKD-EPI 4-level race formula, the fractional excretions of sodium (FeNa) and potassium (FeK), the urine potassium-to-sodium ratio (Na/K urine), and the hemoglobin rate [Hb] were determined for all participants. At the end of IT, eGFR and FeNa increased, respectively, by 22.39% (P<0.01) and 143.85% (P<0.01), but the variation of FeK is not significant (P>0.05). The number of abnormally low eGFR values (<90 mL/min/1.73 m2) was reduced from 11 to 5 (P<0.05). At the end of TP, the eGFR and urine Na-to-K ratio remained on average constant (P>0.05) but FeNa decreased by 96.32% (P<0.001) and FeK increased by 144.41% (P<0.001). The [Hb] rate increased by 9.80% (P<0.001), and players had inadequate hydration practice. The results suggested that in addition to its already known effects, TP preserves the positive effects of IT on glomerular function in athletes preparing for a competition that presents a major challenge.