Volume 101 ·  Issue 42 ·  2021

Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease, and can be life-threatening in severe cases. It is an emergency that every clinician should recognize and master. This paper briefly describes the risk of hyperkalemia in order to pay more attention to hyperkalemia, summarizes the strategies for the treatment of hyperkalemia and reviews different treatment methods, so as to provide ideas for the treatment of hyperkalemia and improve the prognosis of patients.

Hyperkalemia, one of the common complications of patients with chronic kidney disease (CKD), contributes an crucial risk factor affecting the prognosis of patients. The prevention and treatment of hyperkalemia has long been a clinically important topic. This article reviews the diagnosis, treatment and management of CKD combined with hyperkalemia in order to standardize its clinical diagnosis and treatment, achieve early detection, early diagnosis and early treatment, and thus improve the prognosis of patients.

Hyperkalemia is a common complication of heart failure that can lead to severe arrhythmias and even life-threatening. The use of renin-angiotensin-aldosterone system inhibitors (RAASi), beta blockers, low-sodium and high-potassium diets, and the presence of associated comorbidities in patients with heart failure all increase the occurrence of hyperkalemia. In recent years, there have been many new advances in the diagnosis, treatment, prevention and comprehensive management of heart failure complicated with hyperkalemia. To this end, the Heart Failure Group of Cardiovascular Physicians Branch of Chinese Medical Doctors Association organized experts to formulate the "Expert Consensus on the Management of Hyperkalemia in Patients with Heart Failure in China" according to the latest clinical research results at home and abroad, with reference to the relevant consensus issued by the European Society of Cardiology (ESC) in 2018, the Global Organization to Improve the Prognosis of Kidney Disease (KDIGO) in 2020, and the Expert Group of Nephrology Branch of Chinese Medical Association in 2020, combined with China's national conditions and the current situation of heart failure diagnosis and treatment practice, aiming to provide guidance for the prevention, monitoring, diagnosis and treatment and comprehensive management of hyperkalemia in patients with heart failure.

To estimate the prevalence of hyperkalemia and hypokalemia in patients with chronic kidney disease (CKD), analyze the influencing factors and explore the impact on disease prognosis.

A total of 3 190 patients with CKD stage 1-4 from 39 tertiary clinical centers in China between November 2011 and December 2016 were recruited. The baseline characteristics of the patients were collected through face-to-face questionnaire investigation, physical examination and laboratory test. Meanwhile, the data of patient′s end-stage renal disease, cardiovascular disease events and deaths were obtained up to December 2017 through active monitoring. The patients were categorized into three groups based on their baseline level of serum potassium (hypokalemia:<3.5 mmol/L, normal range: 3.5-<5.0 mmol/L, hyperkalemia: ≥5 mmol/L). Multi-nominal logistic regression was employed to evaluate the association between clinical characteristics and the presence of hyperkalemia or hypokalemia. The competing risk-based subdistribution Cox proportional hazards regression was used to assess the association between baseline level of serum potassium and various outcomes.

The mean age of the patients was (50±14) years, with a male rate of 57.6% (1 839/3 190) and a majority of glomerulonephritis (59.7%, 1 668/2 792). Patients with CKD stage 3-4 accounted for 70.8% (2 260/3 190), and the mean level of serum potassium was (4.4±0.7) mmol/L. The prevalence of hypokalemia and hyperkalemia was 3.7% (n=118) and 17.6% (n=561), respectively. In the multivariable adjusted analysis, presence of history of cardiovascular disease (OR=0.33, 95%CI: 0.13-0.83, P=0.019) and estimated glomerular filtration rate (OR=0.95, 95%CI: 0.91-0.98, P=0.001) were inversely associated with hypokalemia, while use of thiazide or loop diuretic (OR=2.06, 95%CI: 1.51-2.81, P<0.001) and estimated glomerular filtration rate (OR=1.13, 95%CI: 1.12-1.16, P<0.001) were positively associated with hyperkalemia. After adjusting for relevant cardiovascular and renal risk factors, the result only showed a significant association between hypokalemia and risk of all-cause mortality (HR=2.12, 95%CI: 1.06-4.24, P=0.034).

Hypokalemia and hyperkalemia were not rare in patients with CKD in China, with the latter more prevalent. Hypokalemia was independently associated with the risk of death.

To investigate the prevalence and associated factors of hyperkalemia in dialysis patients.

Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia.

A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD (OR=2.25, 95%CI: 1.54-3.30), diabetes mellitus (DM) (OR=1.65, 95%CI: 1.17-2.32), high body mass index (BMI) (OR=1.06, 95%CI: 1.03-1.09), high levels of serum albumin (OR=1.04, 95%CI: 1.01-1.07) and phosphorus (OR=3.12, 95%CI: 2.44-4.00), low levels of serum bicarbonate (OR=0.89, 95%CI: 0.87-0.92), triglycerides (OR=0.76, 95%CI: 0.68-0.85) and creatinine (OR=0.95, 95%CI: 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR=1.38, 95%CI: 1.11-1.72) and beta-blocker (OR=1.32, 95%CI: 1.07-1.64) were associated with hyperkalemia.

Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

To investigate the prevalence of hyperkalemia in hospitalized patients, and analyze the effects of different serum potassium levels and change rates of serum potassium on the mortality of hospitalized patients.

The clinical data of 944 446 hospitalized patients in Sichuan Provincial People′s Hospital from January 2009 to December 2018 were retrospectively analyzed. Hyperkalemia is defined as serum potassium ≥ 5.5 mmol/L. The effects of serum potassium level and its change rate on hospitalized mortality were analyzed.

There were 15 771 patients with hyperkalemia, and the prevalence of hyperkalemia was 1.7% (15 771/944 446). However, the discharge diagnosis rate was only 11.0% (1 735/15 771), and the missed diagnosis rate was 89.0% (14 036/15 771). Cox regression analysis showed that serum potassium<3.5 mmol/L (HR=1.338, 95%CI: 1.164-1.537, P<0.001) or ≥ 6.5 mmol/L (HR=1.421, 95%CI: 1.158-1.744, P=0.001) increased the risk of hospitalized mortality compared with patients with normal serum potassium. Compared with the increased rate of serum potassium by 0.01-0.10 mmol/d, patients who reached the peak of serum potassium at admission (HR=1.251, 95%CI: 1.077-1.453, P=0.003), increased rate of serum potassium by 0.11-0.51 mmol/d (HR=1.499, 95%CI: 1.315-1.709, P<0.001) or >0.51 mmol/d (HR=2.431, 95%CI: 2.105-2.807, P<0.001) increased the risk of mortality. Of patients with hyperkalemia, those who did not repeat the serum potassium test had a higher risk of mortality (HR=1.656, 95%CI: 1.434-1.914, P<0.001).

The prevalence of hyperkalemia in hospitalized patients was 1.7%, and the missed diagnosis rate was high at discharge. Patients who had hypokalemia at admission, severe hyperkalemia, rapid increased serum potassium, or failed to repeat serum potassium test during hospitalization, had higher risk of mortality.

To explore the prevalence and related factors of hyperkalemia in patients with diabetic kidney disease (DKD).

DKD patients from the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were selected, and the clinical data of the patients were retrospectively collected. The prevalence of hyperkalemia in DKD patients and the prevalence of hyperkalemia in patients with different age, gender and different stages of chronic kidney disease (CKD) were studied, and the related factors of hyperkalemia were further explored.

A total of 1 721 patients with DKD were included, with 1 117 males (64.9%) [mean age: (56±12) years] and 604 females (35.1%) [mean age: (59±12) years]. The blood potassium level of the study population was (4.93±0.77) mmol/L, in which the serum potassium level of male and female was (4.92±0.77) mmol/L and (4.93±0.76) mmol/L, respectively, and the difference was not statistically significant (P=0.752). Further grouping by CKD stage, the serum potassium levels of CKD stage 1-5 patients were (4.58±0.52), (4.65±0.47), (4.86±0.59), (5.21±0.79) and (5.61±0.88) mmol/L, respectively, and the difference was statistically significant (F=170.701, P<0.001). The prevalence of hyperkalemia was 37.0% (636/1 721). The prevalence of mild, moderate and severe hyperkalemia was 17.4%, 10.5% and 9.1%, respectively. There was no significant difference in the prevalence of hyperkalemia between men and women (36.8% vs 37.3%, χ²=0.035,P=0.851). The prevalence of hyperkalemia in CKD stage 1-5 patients was 16.3%, 21.2%, 37.6%, 55.2%, 72.5%, respectively, which increased with the severity of CKD (χ²=365.721, P<0.001). Multivariate logistic regression showed that estimated glomerular filtration rate (OR=0.975, 95%CI: 0.972-0.979), diastolic blood pressure (OR=0.985, 95%CI: 0.975-0.994) and serum sodium concentration (OR=0.972, 95%CI: 0.945-1.000) were the influencing factors of hyperkalemia in DKD patients.

The prevalence of hyperkalemia in DKD patients was 37.0%. Glomerular filtration rate, diastolic blood pressure and serum sodium concentration were the influencing factors. The serum potassium level and the prevalence of hyperkalemia increased with the deterioration of renal function.

To investigate the prevalence of hyperkalemia and recurrent hyperkalemia in maintenance hemodialysis patients, and identify the related factors.

The general information and clinical data of maintenance hemodialysis patients in the hemodialysis center of the First Affiliated Hospital of Nanjing Medical University from January to December 2020 were collected. According to the level of serum potassium, the patients were divided into normokalemia group and hyperkalemia group. Patients in the hyperkalemia group were further divided into single hyperkalemia group and recurrent hyperkalemia group according to the number of occurrences of hyperkalemia. Then, the prevalence of different serum potassium abnormalities and the related factors were explored.

Among the 352 patients included in the final analysis, 129 cases (36.6%) were in the normokalemia group [mean age: (62±15) years, 99 males] and 223 cases (63.4%) were in the hyperkalemia group [mean age: (60±14) years, 153 males]. Multivariate logistic regression analysis demonstrated that, compared with the normokalemia group, night-time dialysis (OR=4.012, 95%CI: 1.519-10.601, P=0.005), concurrent diabetes (OR=1.947, 95%CI: 1.148-3.304, P=0.013) and the number of serum potassium tested before hemodialysis (OR=1.561, 95%CI:1.292-1.885, P<0.001) were independent risk factors for hyperkalemia. Among 223 patients with hyperkalemia, 78 cases (35.0%) were in single hyperkalemia group and 145 cases (65.0%) were in recurrent hyperkalemia group. Multivariate logistic regression analysis demonstrated that, serum calcium (OR=21.885, 95%CI: 3.740-128.077, P=0.001), peak value of serum potassium before hemodialysis (OR=63.157, 95%CI: 25.265-157.876, P<0.001) and the number of serum potassium tested before hemodialysis (OR=1.814, 95%CI: 1.378-2.388, P<0.001) were the independent risk factors for the recurrence of hyperkalemia.

The prevalence of hyperkalemia is high in maintenance hemodialysis patients, especially in those with diabetes or night-time dialysis. It is necessary to monitor serum potassium regularly. In addition, high serum calcium and peak value of serum potassium before hemodialysis are related factors for recurrent hyperkalemia.

To validate the accuracy and consistency of a previously established prediction model for the occurrence of hyperkalemia in non-dialytic chronic kidney disease (CKD) patients.

All patients diagnosed with CKD from Outpatient Department of Shanghai Changzheng Hospital during the 4th quarter of 2020 were recruited. Demographic data, clinical characteristics and prediction model-related parameters of the patients were collected and analyzed. Receiver operating characteristic (ROC) curve was drawn to evaluate the effectiveness of the model, and the specificity and sensitivity were calculated based on the cut-off value of 4 obtained from the previous model. The improved Hanley method was used to compare the area under the curve (AUC) between the previously established model and current validation dataset. The calibration curve was drawn to verify the model calibration degree.

A total of 434 patients diagnosed with non-dialytic CKD were enrolled, among whom 233 were males and 201 were females, with an average age of (55±16) years. According to the measured serum potassium values, the prevalence of hyperkalemia was 7.6%. And 33 patients were allocated to the hyperkalemia group and 401 patients were to the normal potassium group. There was no significant difference in age and sex between the two groups (both P>0.05). A combination of hyperkalemia and heart failure (27.3% vs 3.7%,P<0.001), diabetes (42.4% vs 19.7%,P=0.002), and acidosis (51.5% vs 7.0%, P<0.001) were more frequently in the hyperkalemia group, compared with the normal serum potassium group. Patients in the hyperkalemia group were more likely to have a past history of serum potassium ≥5.0 mmol/L (48.5% vs 2.5%,P<0.001). For the drugs that could increase serum potassium levels, there was a significant correlation between Chinese herbal medicine and the occurrence of hyperkalemia, while renin-angiotensin-aldosterone system inhibitor (RAASi) and potassium supplementation showed no significant difference between the two groups. The results of ROC curve analysis showed that the AUC was 0.914, with the sensitivity of 84.8% and the specificity of 79.8% with the cut-off value of 4. The difference of AUC between the previously established risk assessment model of hyperkalemia in patients with non-dialytic CKD and current validation dataset was not statistically significant (Z=1.924, P=0.054), indicating the good accuracy and consistency of the prediction model. In the calibration curve, when the predicted risk of patients was below 0.4 or above 0.6, the prediction effect of the model was better.

The previously-constructed hyperkalemia prediction model in non-dialytic CKD patients had good accuracy and consistency, and could be used to evaluate the risk of hyperkalemia in all stages of non-dialytic CKD patients.

To explore risk factors for hyperkalemia in hemodialysis (HD) patients, and establish and verify a risk assessment model of hyperkalemia in HD patients.

The clinical data of HD patients who were admitted to the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University between April 2020 and January 2021 were retrospectively collected and divided into training dataset and validation dataset by using the conversion-random number generator. In the training dataset, multivariate logistic regression analysis was used to screen the risk factors for hyperkalemia in HD patients and the factors were scored to establish the risk assessment model. The validation dataset was substituted into the model and the receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to verify the effectiveness of the risk prediction model in predicting hyperkalemia.

A total of 502 HD patients were enrolled and further divided into training dataset (n=372) and validation dataset (n=130). There were 268 males and 234 females, with a mean age of (54±13) years. Multivariate logistic regression analysis showed that metabolic acidosis, high potassium diet, history of hyperkalemia, the change of electrocardiogram (ECG), disfunction of vascular access and time interval from last dialysis were risk factors for causing hyperkalemia in patients undergoing HD. Risk assessment model was established based on these risk factors. The AUC of the ROC curve was 0.799. Using 5 as the cut-off value, the sensitivity and specificity for predicting hyperkalemia events was 61.4% and 86.3%, respectively.

The current study preliminarily established a risk assessment model for hyperkalemia in HD patients, which can help clinicians manage the potassium level of HD patients.

To investigate the relationship between V444A mutation of the ABCB11 gene and primary intrahepatic stone (PIS).

A total of 164 patients (including 91 males and 73 females, with an average age of (46.0±13.0) years) with PIS and 164 healthy (including 99 males and 65 females, with an average age of (43.8±16.7) years) volunteers were enrolled in this case-control study between October 2017 and June 2019. TaqMan-MGB was used for detecting the V444A polymorphism site of the ABCB11 gene. All the genotypes and allele frequencies were calculated. Pearson chi-squared test was performed to detect the differences in allele and genotype distribution between the two groups. Logistic regression analysis was used to identify genotypes associated with PIS.

There was no significant difference in age and gender between the two groups(both P>0.05). The distributions of V444A allele and genotype accorded with Hardy-Weinberg equilibrium law (P=0.161), which indicated that the selected control group represented statistically acceptable sample. Two alleles of T and C, and three genotypes of TT, TC and CC were detected in the locus of V444A. The T and C allele frequencies in the PIS group and the control group were 28.4% vs 35.4%, and 71.6% vs 64.6%, respectively. The frequencies of the T and C alleles were not different between the two groups (P=0.054). The frequencies of TT, TC and CC genotypes in the two groups were 5.5%, 45.7%, 48.8%, and 14.6%, 41.5%, 43.9%, respectively, with significant difference between the two groups (P=0.023). Logistic regression analysis revealed the V444A polymorphism (TC heterozygous mutation) was associated with PIS.

ABCB11 gene polymorphism at the site of V444A may be related to the susceptibility of PIS.

The clinical manifestations, laboratory and imaging results, diagnosis and treatment and prognosis of 5 patients with mucinous adenocarcinoma of the gallbladder were analyzed. It was found that the clinical characteristics of mucinous adenocarcinoma of the gallbladder were very similar to that of gallbladder malignant tumor, and it was difficult to differentiate. Ultrasound guided gallbladder needle biopsy can confirm the diagnosis before surgery. Surgery is still the first choice of treatment. Since laparoscopic surgery has obvious advantages over open surgery, it is recommended to be preferentially used. If the tumor is under T2 stage and has no aggressive metastasis, the prognosis is generally good.

A patient with hemorrhage of skin and mucosa, hemoptysis, chest pain, thrombocytopenia and pulmonary consolidation was diagnosed with chronic diffuse intravascular coagulation (DIC) combined with pulmonary embolism. The disease was significantly relieved after anticoagulation treatment. DIC is a group of acquired clinical syndromes characterized by activation of coagulation system, increased thrombin production and extensive microthrombosis due to different etiologies. Among them, the onset of chronic DIC is hidden, the course of disease is long, and some laboratory indexes may not change obviously due to compensation, which is difficult to identify and diagnose in clinic.

This article reports an elderly patient with chronic renal failure caused by autosomal dominant polycystic kidney disease, complicated with emphysema and hypertension. Valsartan and amlodipine besylate were given to reduce blood pressure. The blood pressure, renal function and electrolyte control were good in the early stage, but hyperkalemia occurred repeatedly in the later stage. After adjusting a variety of blood pressure lowering drugs, adverse drug reactions such as poor blood pressure control and shortness of breath and ankle edema occurred. Finally, sacubitril, valsartan sodium and amlodipine besylate were selected to synergistically reduce blood pressure, and sodium zirconium cyclosilicate powder was used to reduce potassium. After follow-up, the patient's renal function, blood pressure and blood potassium were well controlled.

This article reports the nutritional management of hyperkalemia in a patient who underwent renal transplantation and intestinal bladder enlargement. Excluding factors such as delayed recovery of transplanted kidney function, bleeding, infection, high potassium dietary intake, etc., the patient's persistent hyperkalemia was related to the absorption of potassium in urine by the ileum at the new bladder, and the blood potassium gradually returned to normal after adhering to a low potassium diet and strengthening urine excretion. The cause of hyperkalemia in this case is rare, and it also alerts clinicians to the risk of electrolyte disorders in the intestinal bladder.

Hemodialysis is an important measure to maintain the life of patients with end-stage renal disease, but hyperkalemia often occurs in patients during dialysis, and serious adverse events such as arrhythmia and sudden cardiac death may occur in severe cases. Therefore, it is very important to pay attention to the concentration of potassium ions in dialysate and adjust the blood potassium level of patients in time. Combined with domestic and foreign literature and clinical experience, this review briefly describes the epidemiology and mechanism of hyperkalemia in dialysis patients, focusing on the prescription of dialysate potassium ion concentration, the correlation between dialysate potassium ion and serum potassium level, the relationship between dialysate potassium ion concentration and arrhythmia and cardiovascular complications, and the relationship between potassium ion concentration and patients' prognosis, so as to attract clinical attention.

Potassium plays a vital role in the normal cell membrane potential. Both hyperkalemia and hypokalemia will affect the electrophysiological conduction of the heart, causing abnormalities in the resting membrane potential of cardiomyocytes, cardiac depolarization and myocardial excitability, causing serious arrhythmia and threatening patients' lives. Potassium balance regulation is mainly dependent on the kidneys, and hyperkalemia and hypokalemia tend to occur when kidney disease is present. Although arrhythmias due to hyperkalemia and hypokalemia have been associated with higher short-term all-cause mortality in previous observational studies, few studies have reported the long-term effects of abnormal blood kalemia on cardiovascular disease-related mortality, and there is a lack of exploration of long-term outcomes of renal disease.

Acute kidney injury and chronic renal failure are very common in hospitalized patients. Therefore, in order to better judge the prognosis of disease, more accurate predictive indicators are needed to guide clinical practice. The study enrolled a total of 1,538 inpatients in a multicenter prospective cohort study. During the 3-month outpatient follow-up, patients' urine was collected for monocyte chemotactic protein (MCP-1/CCL2), uromodulin (UMOD) and human chitinase 3-like protein 1 (CHI3L1). The median follow-up time was 4.3 years to assess the relationship between biomarker levels and glomerular filtration rate and renal outcome combined events (incidence, progression, and end-stage renal disease of chronic renal failure). At the same time, the results of these clinical studies were validated in the mouse model of renal atrophy and renal repair to further clarify the role of these molecular markers in the progression of renal disease.

Several studies have confirmed the existence of autophagy dysregulation in diabetic nephropathy, but its underlying pathological mechanism is not clear. Through the analysis of kidney tissues of diabetic mice and diabetic patients, the study found that autophagy was significantly inhibited in the kidneys. Specific knockout of the autophagy-related gene Atg6 in the proximal tubules of mice kidney can inhibit autophagy, lead to kidney hypertrophy in diabetic mice, aggravate tubular damage, inflammatory reaction and fibrosis, and finally lead to increased proteinuria, indicating that autophagy plays a protective role in diabetic nephropathy. At the same time, it was found that small RNA214 (miR-214) expression was upregulated in diabetic tissues, thereby inhibiting the expression of downstream UNC-51-like autophagy-related activating enzyme (ULK1), ultimately leading to a decrease in autophagy expression. Specific silencing of the expression of miR-214 in the proximal tubules of the kidney reduced the inhibition of ULK1, prevented the increase of kidney size in diabetic nephropathy, and reduced the level of proteinuria. Furthermore, p53 and miR-214 were highly expressed in kidney tissues of diabetic patients compared to non-diabetic samples. Blocking the expression of p53 can increase ULK1 and autophagy levels, thereby favoring the improvement of diabetic nephropathy. The study also found that p53/miR-214 was positively associated with renal fibrosis, while ULK1/LC3 was inversely associated with renal fibrosis in diabetic patients. Therefore, the final results of this study confirmed the role of p53/miR-214/ULK1 axis-regulated autophagy in kidney tissue of diabetic patients, providing a new target for clinical treatment of diabetic nephropathy.