TTKG Research Articles

#2026 Hypokalemia associated to neuroendocrine carcinoma of the cervix

Abstract Background and Aims Hypokalemia is one of the most common electrolyte disorders seen in clinical practice. Hypokalemia can be caused by decreased intake of potassium, redistribution of potassium (K+) in cells or by excessive gastrointestinal losses or renal losses. In this setting, hypokalemia may also be caused by the paraneoplastic production of ectopic adrenocorticotropic hormone (ACTH) by some tumors. Cancer of the uterine cervix is the fourth common cancer affecting women worldwide and the fourth most common gynecologic cancer in Spain. Neuroendocrine carcinoma of the cervix represents about 2% of all cervical neoplasms. Method We report the case of a 44-year-old Peruvian woman with hypokalemia who was diagnosed with Cushing syndrome secondary to paraneoplastic production of ACTH by neuroendocrine carcinoma of cervix. Results Patient was overweight and affected by uterine myoma and anemia without further investigations. She was admitted to our hospital due to lower back pain, leg swelling and constipation. Blood pressure was normal, chest radiography did not show abnormal findings and ECG showed the U wave. Laboratory tests at admission revealed hypokalemia (2.3 mmol/L), metabolic alkalosis, anemia (hemoglobin 9.5 g/dL), hyperkaliuria (K+ urine/Creatinine urine 70 mmol/g) with an elevated transtubular potassium gradient (TTKG=12) and normal renal function. Laboratory data are presented in Table 1. She developed hypertension in the first day of hospitalization. Renin, aldosterone and cortisol tests was performed. Hypercortisolism was observed and confirmed with 24-hour urinary cortisol excretion. Because of an elevated ACTH (263 pg/mL), pituitary magnetic resonance imaging was performed without lesions. Whole-body computed tomography revealed a cervical mass. PET scan showed pelvic, adrenal, hepatic and local lymphadenopathy activity (see Fig. 1). After the histopathological study, diagnostic of small cell neuroendocrine carcinoma of the cervix was made. Chemotherapy therapy was initiated with cisplatin/etoposide regimen. The patient decide to return to Peru because of the poor prognosis of her illness. At discharge, potassium level was 3 mmol/L despite the treatment with spironolactone, ramipril, losartan and oral potassium chloride (160 mmol). Conclusion Hypokalemia is a common clinical disorder. In some patients it may be caused by an increased mineralocorticoid activity due to ectopic ACTH-secreting tumors. Applying diagnostic algorithms to electrolyte disorders, beyond their simple treatment, can unmask secondary causes and serious diseases.

Isolated hypoaldosteronism is a cause of hypovolemic but not euvolemic hyponatremia.

Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease's spectrum. In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia. Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+. Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity. Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

Bartter Syndrome: A Case Report

Background: Bartter's syndrome refers to a group of genetic disorders that affect the renal tubular system, which is responsible for reabsorbing various substances such as sodium, potassium, and chloride from the urine into the blood. This study aimed to present a clinical case related to Bartter syndrome.
 Case presentation: A 52-year-old male patient in the internal medicine department of Dr. M. Djamil General Hospital Padang with the main complaint of weakness in both legs increasing since 1 day ago. On laboratory examination, the patient found potassium 1.7 mmol/L, indicating hypokalemia. Renal function examination showed normal kidney function. Examination of blood gas analysis showed results of metabolic alkalosis. Examination of urine potassium obtained potassium levels of 22 mmol/day, urine osmolarity of 140 mOsm/kgH2O at serum osmolarity of 274 mOsm/kgH2O, with TTKG (transtubular potassium gradient) = 28. The patient was diagnosed with Bartter syndrome. Treatment is carried out by administering KSR tablets 3x600 mg orally while monitoring electrolytes regularly.
 Conclusion: This patient has hypokalemia, metabolic alkalosis, normal magnesium and calcium, and hypercalciuria. This patient is diagnosed with Bartter syndrome.

Diagnostic predictivity of transtubular potassium gradient for primary hypoadrenocorticism in hyperkalemic dogs: a cross-sectional study.

Transtubular potassium gradient has never been evaluated in the diagnosis of primary hypoadrenocorticism in dogs. The objective of this study is to evaluate the diagnostic utility of transtubular potassium gradient for the diagnosis of primary hypoadrenocorticism in dogs with serum K+ > 5.5 mol/L. Cross-sectional study including dogs with primary hypoadrenocorticism and dogs with other disease. Differences in signalment and laboratory parameters between groups were assessed by binary logistic regression modelling. Variables significantly associated with primary hypoadrenocorticism were evaluated for their diagnostic accuracy of this condition by receiver operator characteristic curve analysis and by multivariable logistic regression analysis, respectively. Dogs with primary hypoadrenocorticism (n=39) were significantly younger than hyperkalemic dogs without primary hypoadrenocorticism (n=41). Moreover they had higher serum and urinary concentrations of Na+ and Na+ :K+ , but lower transtubular potassium gradient than hyperkalemic dogs without hypoadrenocorticism. Serum Na+ (sNa+ ) had the highest diagnostic accuracy (area under the curve [AUC]: 0.87, 95% confidence interval, 0.78 to 0.96), followed by the transtubular potassium gradient (AUC: 0.81, 0.72 to 0.91), however the accuracy of the two AUCs was not statistically different. The transtubular potassium gradient-sNa+ additive index (i.e. transtubular potassium gradient+sNa+ /10) had a greater accuracy (AUC: 0.88, 0.79 to 0.94) than transtubular potassium gradient or sNa+ , although it was not statistically superior to the latter. The multivariable logistic regression model showed that transtubular potassium gradient (adjusted odds ratio [aOR]: 0.51, 0.3 to 0.84), sNa+ (aOR: 0.86, 0.78 to 0.95) and spayed female (aOR: 24.96, 2.32 to 267.66) were associated with primary hypoadrenocorticism. Transtubular potassium gradient-sNa+ additive index can contribute to decision-making on diagnosis of primary hypoadrenocorticism in dogs presenting with hyperkalaemia.

Early detection of glomerular dysfunction and renal tubulopathy in children with sickle cell disease in India

Sickle cell disease causes microvascular occlusion in different vascular beds. In kidneys, it leads to occult glomerular dysfunction causing asymptomatic microalbuminuria, proximal tubulopathy causing hyposthenuria and increased free water loss and distal tubulopathy causing poor urine acidification. We studied the prevalence of various types of renal dysfunction, the ability of different tests to detect it at an early stage and the correlation of these parameters in children receiving hydroxyurea (HU). Fifty-six children (sample size calculated using SAS9.2 package) attending paediatric clinical services in a tertiary care hospital between 2 and 12 years of age diagnosed by high-performance liquid chromatography (HPLC) were enrolled. Their demographic and laboratory data including renal and urine parameters were collected. Parameters like fractional excretion of sodium (FeNa), trans tubular potassium gradient (TtKg) and free water clearance (TcH2O) were derived by calculations. Data were analysed using IBM SPSS Version 21.0 and Microsoft Office Excel 2007. We found a significant number of children to have microalbuminuria (17.8%), hyposthenuria (30.4%) and impaired renal tubular potassium excretion (TtKg) (81.3%). A significant correlation was found between the dose of HU with urine osmolality (p < 0.0005) and free water clearance (p = 0.002), while all parameters showed a significant correlation with compliance with HU. Derangement in urine microalbumin and TcH2O correlated significantly with low mean haemoglobin levels (<9 g/dl). Renal dysfunction is common in children with SCD and can be detected early using simple urine parameters and can be prevented with an early and appropriate dosage of HU with good compliance.

Transtubular Potassium Gradient in Hypertensive Emergency

Transtubular Potassium Gradient in Hypertensive Emergency

A RARE BUT WORRYING SIDE EFFECT OF MINERALOCORTICOIDS

TOPIC: Education, Research, and Quality Improvement TYPE: Medical Student/Resident Case Reports INTRODUCTION: Corticosteroids are anti-inflammatory drugs that are known to have multiple side effects. Fludrocortisone, a synthetic mineralocorticoid that lacks glucocorticoid effect, is used in the treatment of hypoaldosteronism but like other corticosteroids is not known to have significant catabolic activity. CASE PRESENTATION: A 58 year old male with hypertension, chronic kidney disease (stage 4) and seizure disorder was admitted for management of persistent hyperkalemia. Initially, serum potassium was 6.2 with BUN of 58 and creatinine of 4.3. Physical exam was negative for orthostatic hypotension. Transtubular potassium gradient (TTKG) during hyperkalemia was calculated to be 3 which pointed to the diagnosis of hypoaldosteronism. Fludrocortisone (FD) was initiated, and potassium level was noted to be trending down and renal function improved to baseline. In the following days, serum chemistry revealed a normal potassium level but a significant rise in BUN, reported to be as high as 102mg/dl. During this period estimated glomerular filtration rate (eGFR) continued to be at baseline, between 20 and 22. Other factors that can cause uremia were ruled out and it was decided to discontinue FD. A significant drop in BUN level was observed, reaching as low as 60. After FD was stopped, a subsequent rise in potassium level was seen which resolved with dietary modifications. DISCUSSION: Fludrocortisone (FD) is a potent mineralocorticoid but has a weak glucocorticoid activity, hence is not known to cause uremia. It is known for treating chronic hyperkalemia in patients with hypoaldosteronism and interdialytic hyperkalemia in ESRD patients. According to a study by Norcliffe-Kaufmann et al., it was reported that patients with FD were found to have higher BUN levels compared to control subjects. For our patient`s persistent hyperkalemia due to hypoaldosteronism, FD was started but subsequently a significant rise in BUN, without changes in renal function, was observed. Uremia can cause debilitating symptoms like extreme fatigue, loss of appetite, headache, nausea and vomiting. In our case, after FD was discontinued a marked drop in BUN and a concomitant increase in potassium were seen. Patient was counseled for strict adherence to low potassium diet which resolved his problem. CONCLUSIONS: In conclusion, since FD has concerning side effects, it should be prescribed with caution in patients with CKD and serial serum chemistry should be followed for abnormalities. Patients, who are taking FD, presenting with uremia and stable renal function should have FD use investigated as one of the underlying cause. For persistent hyperkalemia, other interventions like dietary modification and/or potassium binder can be considered since FD can cause other abnormalities. REFERENCE #1: Dobbin, S., Petrie, J. R., Lean, M., & McKay, G. A. (2017). Fludrocortisone therapy for persistent hyperkalaemia. Diabetic medicine : a journal of the British Diabetic Association, 34(7), 1005–1008. https://doi.org/10.1111/dme.13359 REFERENCE #2: Disorders of Potassium Metabolism. (2011, January 1). ScienceDirect. https://linkinghub.elsevier.com/retrieve/pii/B9781416066408000075 REFERENCE #3: Norcliffe-Kaufmann, L., Axelrod, F. & Kaufmann, H. Developmental abnormalities, blood pressure variability and renal disease in Riley Day syndrome. J Hum Hypertens 27, 51–55 (2013). https://doi.org/10.1038/jhh.2011.107 DISCLOSURES: no disclosure on file for Kisra Anis; no disclosure on file for Zinobia Khan; No relevant relationships by Dileep Kumar, source=Web Response No relevant relationships by Shahzad Shallwani, source=Web Response

Hypokalaemic paralysis and metabolic alkalosis in a patient with Sj\xf6gren syndrome: a case report and literature review

BackgroundAcquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome.Case presentationA 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery.ConclusionsAcquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome.

Association between the transtubular potassium gradient and progression of chronic kidney disease: results from KNOW-CKD.

The transtubular potassium gradient which reflects potassium secretion by the kidney through the cortical collecting duct, has not yet been tested as a surrogate marker of kidney function decline. Here, we investigate the relationship between the transtubular potassium gradient and chronic kidney disease (CKD) progression. We studied 1672 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. Thetranstubular potassium gradient was calculated using a standard equation. The study endpoint was CKD progression, defined as a composite of a ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from baseline values or end-stage kidney disease. During a median follow-up of 4.1years (7149 person-years), 441 participants reached the endpoint. In cause-specific competing risk analysis, the highest tertile was associated with a significantly lower risk of an adverse kidney outcome compared with the lowest tertile [hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.97]. When the transtubular potassium gradient was treated as a continuous variable, an increase of 1 in thetranstubular potassium gradient was associated with a 6% lower risk of CKD progression (95% CI, 0.90-0.99). This association was particularly evident in patients with an eGFR ≥ 45mL/min/1.73 m2. A time-updated transtubular potassium gradient model showed similar results. The predictive performance of the transtubular potassium gradient was significantly less than that of the eGFR, but similar to that of proteinuria, serum bicarbonate, and urine osmolality. A highertranstubular potassium gradient is associated with a significantly lower risk of CKD progression, suggesting that it may offer insights into the prognosis of CKD.

Electrolyte Disturbances in SARS-CoV-2 Infection.

The global pandemic secondary to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to unprecedented global morbidity and mortality. With a bewildering array of complications, renal involvement in various forms is common, including serum electrolyte derangements. Hypokalaemia secondary to SARS-CoV-2 was common in a reported Chinese cohort. Here we review the emerging evidence on hypokalaemia and SARS-CoV-2 infection, the potential pathophysiological mechanisms based on early clinical and histopathological data and important clinical implications. Mechanisms of hypokalaemia are multifactorial and so the electrolyte disturbance can be difficult to avoid. We provide further support to the theory of renin-angiotensin-aldosterone (RAS) activation, discuss the strengths and weaknesses of implicating RAS involvement and highlight the importance of calculating the transtubular potassium gradient to identify those at risk of hypokalaemia and its complications.

Electrolyte Disturbances in SARS-CoV-2 Infection

The global pandemic secondary to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to unprecedented global morbidity and mortality. With a bewildering array of complications, renal involvement in various forms is common, including serum electrolyte derangements. Hypokalaemia secondary to SARS-CoV-2 was common in a reported Chinese cohort. Here we review the emerging evidence on hypokalaemia and SARS-CoV-2 infection, the potential pathophysiological mechanisms based on early clinical and histopathological data and important clinical implications. Mechanisms of hypokalaemia are multifactorial and so the electrolyte disturbance can be difficult to avoid. We provide further support to the theory of renin-angiotensin-aldosterone (RAS) activation, discuss the strengths and weaknesses of implicating RAS involvement and highlight the importance of calculating the transtubular potassium gradient to identify those at risk of hypokalaemia and its complications.

SARS-CoV-2 and hypokalaemia: evidence and implications

The global pandemic secondary to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to unprecedented global morbidity and mortality. With a bewildering array of complications, renal involvement in various forms is common, including serum electrolyte derangements. Hypokalaemia secondary to SARS-CoV-2 was common in a reported Chinese cohort. Here we review the emerging evidence on hypokalaemia and SARS-CoV-2 infection, the potential pathophysiological mechanisms based on early clinical and histopathological data and important clinical implications. Mechanisms of hypokalaemia are multifactorial and so the electrolyte disturbance can be difficult to avoid. We provide further support to the theory of renin-angiotensin-aldosterone (RAS) activation, discuss the strengths and weaknesses of implicating RAS involvement and highlight the importance of calculating the transtubular potassium gradient to identify those at risk of hypokalaemia and its complications.

Transtubular potassium gradient predicts kidney function impairment after adrenalectomy in primary aldosteronism.

Background:In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy.Methods:In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass.Results:In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy.Conclusions:TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

Clinical features, genetic background, and outcome in infants with urinary tract infection and type IV renal tubular acidosis.

Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking. Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up. The study cohort included 12 infants (9 males, age 1-8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645T>G (S549A), c.538G>A (V180I), and c.1-2C>G, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring. Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.

SAT-072 Recurrent Hypokalemic Paralysis: A Case Of Delayed Diagnosis Of Primary Hyperaldosteronism

Introduction: Acute hypokalemic paralysis is a relatively rare, potentially life threatening but treatable cause of acute myopathy. Rapid diagnosis with appropriate treatment is critical. Herein, we present a case of hypokalemic paralysis due to primary hyperaldosteronism. Case report: A 54-year-old Caucasian male with history of HIV on Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir), well controlled HTN on Amlodipine 10 mg and Valsartan 160 mg daily, and pre-diabetes presented to hospital with muscle twitching followed by acute flaccid paralysis of legs. He denied having nausea, vomiting, diarrhea or the use of laxative, diuretics and licorice. No predisposing factors for paralysis were present and there was no family history of periodic paralysis. Over the last 6 months prior to presentation, he had multiple such episodes of generalized weakness and losing the ability to stand up, which typically lasted for few minutes to hours and resolved spontaneously. He had experienced two episodes of pre-syncope. He had multiple ER visits for these episodes, he was started on potassium chloride (unknown dose), but the cause for hypokalemia was not investigated. At presentation, his vitals were stable. Physical exam was significant for generalized decrease in muscle strength (4/5 in all extremities). His laboratory tests revealed: hypokalemia of 2.4 mmol/L (n.3.5-5.1) and alkalosis with bicarbonate of 36mmol/L (n.22-29). Serum magnesium, TSH and cortisol level were normal. His trans-tubular potassium gradient was elevated at 8.4, and urine pH was elevated at 8.0 (n.5-7). With aggressive IV potassium chloride replacement his symptoms resolved. Endocrine investigations revealed elevated aldosterone level (PAC) 42ng/dl (n.4-31) and undetectable plasma renin activity <0.1 ng/ml/hr (n.0.2-1.6). Based on these labs, primary hyperaldosteronism was diagnosed and confirmed by saline suppression test. CT abdomen was negative for adrenal mass. Conclusion: Based on pathophysiology, hypokalemic paralysis is divided into 2 groups: hypokalemic periodic paralysis due to acute shift of potassium into cells, and hypokalemic non-periodic paralysis resulting from a large total body deficit of potassium. 25% of cases of hypokalemic paralysis are secondary to hypokalemic non-periodic paralysis associated with chronic alcoholism, diuretic use, anorexia/bulimia nervosa, renal tubular acidosis, primary hyperaldosteronism, and Gitelman syndrome. Patients with hypokalemic non-periodic paralysis require much higher doses of KCL to recover than those with hypokalemic periodic paralysis. In the setting of hypertension and hypokalemia, either diuretic induced or spontaneous, evaluation for primary hyperaldosteronism should be considered. In the setting of suppressed renin, hypokalemia and PAC > 20 ng/dL, confirmatory testing can be deferred.

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

BackgroundGuidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD.MethodsA total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline.ResultsPatients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (β = − 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07–1.55; P = 0.007).ConclusionsHigh activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.

Maintained Hydration Status After a 24-h Winter Mountain Running Race Under Extremely Cold Conditions.

Background: To date, no study has examined the hydration status of runners competing in a 24-h winter race under extremely cold environmental conditions. Therefore, the aim was to examine the effect of a 24-h race under an average temperature of -14.3°C on hydration status.Methods: Blood and urine parameters and body mass (BM) were assessed in 20 finishers (women, n = 6; men, n = 14) pre- and post-race.Results: Five (25%) ultra-runners had lower pre-race plasma sodium [Na+] and 11 (52%) had higher pre-race plasma potassium [K+] values than the reference ranges. Post-race plasma [Na+], plasma osmolality, urine osmolality and urine specific gravity remained stable (p > 0.05). The estimated fluid intake did not differ (p > 0.05) between women (0.30 ± 0.06 L/h) and men (0.46 ± 0.21 L/h). Runners with a higher number of completed ultra-marathons (r = -0.50, p = 0.024) and higher number of training kilometers (r = -0.68, p = 0.001) drank less than those with lower running experience. Pre-race and post-race plasma [Na+] were related to plasma osmolality (r = 0.65, p = 0.002, r = 0.69, p < 0.001, respectively) post-race, but not to fluid intake (p > 0.05). BM significantly decreased post-race (p = 0.002) and was not related to plasma [Na+] or fluid intake (p > 0.05). Post-race hematocrit and plasma [K+] decreased (p < 0.001) and transtubular potassium gradient increased (p = 0.008). Higher pre-race plasma [K+] was related to higher plasma [K+] loss post-race (p = -0.85, p < 0.001).Conclusion: Hydration status remained stable despite the extremely cold winter weather conditions. Overall fluid intake was probably sufficient to replenish the hydration needs of 24-h runners. Current recommendations may be too high for athletes competing in extremely cold conditions.

Renal potassium handling in carriers of the Gly40Ser mutation of the glucagon receptor suggests a role for glucagon in potassium homeostasis

Plasma potassium concentration (PK) is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. Previous studies in rats showed that glucagon infusion increased urinary potassium excretion dose‐dependently and reversibly. This prompted us to investigate the possible influence of glucagon on potassium handling in humans. We took advantage of the Gly40Ser mutation of the glucagon receptor (GR) that results in a partial loss of function of the GR. In the Olivetti cohort (male workers), 25 subjects who carried this mutation were matched 1:4 to 100 noncarriers for age and weight. Estimated osmolarity of serum and 24‐h urine (Sosm and Uosm, respectively) was calculated from the concentrations of the main solutes: [(Na+K)*2 + urea (+glucose for serum)]. Transtubular potassium gradient (TTKG), reflecting the intensity of K secretion in the distal nephron, was calculated as [(urine K/serum K)(Uosm/Sosm)]. There was no significant difference in serum K, or 24‐h urine urea, Na and K excretion rates. But urine K concentration was significantly lower in carriers than in noncarriers. Means (interquartile range): 38 (34–43) versus 47 (43–51) mmol/L, P = 0.030. TTKG was also significantly lower in carriers: 4.2 (3.9–4.6) versus 5.0 (4.7–5.2), P = 0.015. This difference remained statistically significant after adjustments for serum insulin and 24‐h Na and urea excretions. These results in humans suggest that glucagon stimulates K secretion in the distal nephron. Thus, in conjunction with insulin, glucagon may also participate in K homeostasis by promoting renal K excretion.

Fluid Metabolism in Athletes Running Seven Marathons in Seven Consecutive Days

Purpose: Hypohydration and hyperhydration are significant disorders of fluid metabolism in endurance performance; however, little relevant data exist regarding multi-stage endurance activities. The aim of the present study was to examine the effect of running seven marathons in 7 consecutive days on selected anthropometric, hematological and biochemical characteristics with an emphasis on hydration status.Methods: Participants included 6 women and 20 men (age 42.6 ± 6.2 years). Data was collected before day 1 (B1) and after day 1 (A1), 4 (A4), and 7 (A7).Results: The average marathon race time was 4:44 h:min (ranging from 3:09 – 6:19 h:min). Plasma sodium, plasma potassium and urine sodium were maintained during the race. Body mass (p < 0.001, η2 = 0.501), body fat (p < 0.001, η2 = 0.572) and hematocrit (p < 0.001, η2 = 0.358) decreased. Plasma osmolality (Posm) (p < 0.001, η2 = 0.416), urine osmolality (Uosm) (p < 0.001, η2 = 0.465), urine potassium (p < 0.001, η2 = 0.507), urine specific gravity (Usg) (p < 0.001, η2 = 0.540), plasma urea (PUN) (p < 0.001, η2 = 0.586), urine urea (UUN) (p < 0.001, η2 = 0.532) and transtubular potassium gradient (p < 0.001, η2 = 0.560) increased at A1, A4, and A7 vs. B1. Posm correlated with PUN at A1 (r = 0.59, p = 0.001) and A4 (r = 0.58, p = 0.002). The reported post-race fluid intake was 0.5 ± 0.2 L/h and it correlated negatively with plasma [Na+] (r = −0.42, p = 0.007) at A4 and (r = −0.50, p = 0.009) at A7. Uosm was associated with UUN at A1 (r = 0.80, p < 0.001), at A4 (r = 0.81, p < 0.001) and at A7 (r = 0.86, p < 0.001) and with Usg (r = 0.71, p < 0.001) at A1, (r = 0.52, p = 0.006) at A4 and (r = 0.46, p = 0.02) at A7.Conclusions: Despite the decrease in body mass, fluid and electrolyte balance was maintained with no decrease in plasma volume after running seven marathons in seven consecutive days. Current findings support the hypothesis that body mass changes do not reflect changes in the hydration status during prolonged exercise.

A Practical Approach for Pathophysiological Diagnosis of Refractory Hypokalemia

Hypokalemia is a common finding in hospitalized patients. In most cases the cause will be obvious. However, in a subgroup of patients the cause is occasionally uncertain and establishing the diagnosis may present difficulties and can become a challenge. In such cases, measurement of urinary indices e.g. trans-tubular potassium gradient [TTKG] and random urine potassium/creatinine concentrations along with blood acid/base parameters and assessment of urinary excretion of potassium, chloride, calcium and creatinine have been employed in the differential diagnosis. TTKG and urine potassium/creatinine ratio are used as a rapid appropriate index of potassium excretion and to establish a proper diagnosis and management in this medical emergency. It helps to differentiate between hypokalemia caused by redistribution or renal potassium wasting. Urinary chloride excretion and urinary calcium/creatinine ratio in conjunction with plasma acid/base values, aldosterone, renin and cortisol values are used for narrowing the differential diagnosis of refractory hypokalemia. Conclusions: Calculating the trans-tubular potassium concentration gradient, urinary potassium/creatinine ratio, urinary chloride excretion and urinary calcium/creatinine ratio in conjunction with plasma acid/base values provided simple and reliable tests for differential diagnosis of causes of refractory hypokalemia and to provide a proper management in the intensive care unit and in the emergency until advanced further tests to be done.