Understudied Hyperphosphatemia (Chronic Kidney Disease) Treatment Targets and New Biological Approaches.

Hyperphosphatemia is a secondary disorder of chronic kidney disease that causes vascular calcifications and bone-mineral disorders. As per the US Centers for Disease Control and Prevention, renal damage requires first-priority medical attention for patients with COVID-19; according to a Johns Hopkins Medicine report, SARS-CoV-2 can cause renal damage. Therefore, addressing the research inputs required to manage hyperphosphatemia is currently in great demand. This review highlights research inputs, such as defects in the diagnosis of hyperphosphatemia, flaws in understanding the mechanisms associated with understudied tertiary toxicities, less cited adverse effects of phosphate binders that question their use in the market, socioeconomic challenges of renal treatment and public awareness regarding the management of a phosphate-controlled diet, novel biological approaches (synbiotics) to prevent hyperphosphatemia as safer strategies with potential additional health benefits, and future functional food formulations to enhance the quality of life. We have not only introduced our contributions to emphasise the hidden aspects and research gaps in comprehending hyperphosphatemia but also suggested new research areas to strengthen approaches to prevent hyperphosphatemia in the near future.

Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19.

Background: Persistent hyperkalemia (hyperK) and hyperphosphatemia (hyperP) despite renal replacement therapy (RRT) was anecdotally reported in COVID-19 and acute kidney injury (AKI) requiring RRT (CoV-AKI-RRT). However, observation bias could have accounted for the reports. Thus, we systematically examined the rate and severity of hyperK and hyperP in patients with CoV-AKI-RRT in comparison with the pre-COVID-19 era. Methods: We identified patients with CoV-AKI-RRT treated with sustained low-efficiency dialysis (SLED) for ≥2 days in March-April 2020. As pre-COVID-19 control, we included patients with AKI treated with SLED in December 2019. We examined the rates of hyperK (serum potassium [sK] ≥5.5 mEq/L), severe hyperK (sK ≥6.5 mEq/L), hyperP (serum phosphate [sP] ≥4.5 mg/dl), and moderate or severe hyperP (sP ≥7-10 and >10 mg/dl, respectively) as %SLED-days with an event. Results: Along the duration of SLED, the incidence of hyperK was greater in CoV-AKI-RRT (n=64; mean 19%±2% versus 14%±3% SLED-days, P=0.002) compared with control (n=60). The proportion of patients with one or more event of severe hyperK was greater in CoV-AKI (33% versus 7%, P<0.001). The incidence of hyperP was similar between groups (mean 56%±4% versus 53%±5% SLED-days, P=0.49). However, the proportion of patients with one or more event of moderate and severe hyperP was greater in CoV-AKI-RRT (86% versus 60%, P=0.001, and 50% versus 18%, P<0.001, respectively). Among those with CoV-AKI-RRT, sK and sP correlated with lactate dehydrogenase (LDH; r=0.31, P=0.04, and r=0.31, P=0.04, respectively), whereas hyperP also correlated with shorter SLED runs (hours/run; r=-0.27, P=0.05). Conclusions: Refractory hyperK and hyperP were more frequent in CoV-AKI-RRT compared with the pre-COVID-19 era. Because of the correlation of sK and sP with higher LDH and sP with shorter SLED runs, intracellular ion release from cell injury due to cytokine storm and RRT interruptions may account for the findings.

Effect of Electrolyte Imbalance on Mortality and Late Acute Kidney Injury in Hospitalized COVID-19 Patients.

INTRODUCTION: As a multisystem illness, Coronavirus disease 2019 (COVID-19) can damage different organs. This study investigated the effect of electrolyte imbalance (EI), with or without concomitant renal dysfunction, on the prognosis of COVID-19 in hospitalized patients. METHODS: We evaluated 499 hospitalized patients with confirmed COVID-19, without a history of chronic kidney disease. The patients' demographic data, laboratory values, and outcomes were retrospectively collected from the hospital information system. Serumelectrolytes including sodium, potassium, magnesium, calcium, and phosphorus abnormalities were analyzed on admission and during the hospitalization period. The outcomes of this study were the occurrence of acute kidney injury (AKI) after the first week of hospitalization and in-hospital mortality rate. Multivariate analyses were carried out to obtain the independent risk of each EI on mortality, by adjusting for age, gender, and AKI occurrence. RESULTS: Among the 499 COVID-19 patients (60.9% male), AKI occurred in 168 (33.7%) and mortality in 92 (18.4%) cases. Hypocalcemia (38%) and hyponatremia (22.6%) were the most prevalent EIs, and all EIs were more common in the AKI group than in the non-AKI group. Hyponatremia (Adjusted Odds ratio [AOR] = 2.34, 95% CI: 1.30 to 4.18), hypernatremia (AOR = 8.52, 95% CI: 1.95 to 37.32), and hyperkalemia (AOR = 4.63, 95% CI: 1.65 to 13) on admission were associated with poor prognosis. Moreover, hyponatremia (AOR = 3.02, 95% CI: 1.28 to 7.15) and hyperphosphatemia (AOR = 5.12, 95% CI: 1.24 to 21.09) on admission were associated with late AKI occurrence. CONCLUSION: This study highlights the role of hyponatremia, hypernatremia, hyperkalemia, and hyperphosphatemia in poor prognosis of COVID-19. According to the independent effect of EI on late AKI and mortality, we recommend physicians to raise awareness to closely monitor and correct EI during hospitalization.  DOI: 10.52547/ijkd.6904.

Hypermagnesemia and hyperphosphatemia are highly prevalent in patients with COVID-19 and increase the risk of death.

OBJECTIVES: Nonrespiratory manifestations of COVID-19 include endocrine disorders, among which are calcium-magnesium-phosphate homeostasis abnormalities, which seem to influence the disease severity and patient outcome. The aim of this study was to evaluate the prevalence and impact of calcium-magnesium-phosphate and vitamin D3 disorders on survival in patients hospitalized for COVID-19 depending on the severity of the disease and kidney function. DESIGN OR METHODS: The study was conducted between April 2020 and May 2021 at Central Clinical Hospital in Warsaw, Poland. A total of 146 patients who had tested concentration of at least one of the studied elements, estimated glomerular filtration ratio, creatinine levels, and blood saturation, and were diagnosed with COVID-19 disease were included in the analysis. RESULTS: We found that hypermagnesemia was common and associated with a 1.5-fold increased risk of death in the whole cohort. Hyperphosphatemia also increased the risk of death, exactly 2.4-fold. Furthermore, we found a statistically significant association between increased mortality in the whole cohort and hypovitaminosis D3 (P <0.05). Serum creatinine concentration and estimated glomerular filtration ratio significantly correlated with serum magnesium and phosphate levels. CONCLUSION: Hypermagnesemia, hyperphosphatemia, and hypovitaminosis D but not hypocalcemia influence the mortality of patients with COVID-19. These parameters should be monitored routinely in this group of patients, especially in those with decreased kidney function.

Dietary Advice in Hemodialysis Patients: Impact of a Telehealth Approach During the COVID-19 Pandemic.

OBJECTIVE: The purpose of this study was to assess the effect of a telehealth-delivered nutritional intervention via telephone in maintenance hemodialysis (HD) patients during the coronavirus outbreak. METHODS: This was a multicenter, observational, prospective, and longitudinal study of 156 patients undergoing maintenance HD from 15 dialysis units conducted during the COVID-19 pandemic. We assigned patients to receive dietary counseling through a phone call, according to their biochemical and nutritional parameters. Dry weight, intradialytic weight gain percentage (%IDWG), body mass index, potassium, phosphorus, calcium, calcium/phosphorus product, normalized protein catabolic rate, albumin, and hemoglobin were recorded at baseline and 1 month after nutrition counseling. RESULTS: The prevalence of hyperkalemia and hyperphosphatemia decreased significantly after dietary advice. A statistically significant reduction in serum potassium and phosphorus levels was observed in patients receiving counseling for hyperkalemia and hyperphosphatemia. In addition, there was a statistically significant decrease in the prevalence of hypophosphatemia. We also observed a significant decrease in %IDWG, although no statistically significant differences were detected in patients with high %IDWG. The data demonstrated statistically significant differences in potassium and phosphorus values when the person receiving the phone contact was the patient or the caregiver. The main statistically significant differences in hypophosphatemia %IDWG were only observed when contact was made directly with the patient. No differences were observed when the contact was made through nursing homes. CONCLUSION: Our results suggest that telehealth-delivered dietary interventions can improve the clinical and nutritional parameters of HD patients. Consequently, this strategy may be effective for promoting continuous nutritional monitoring in these patients, in particular when conducting a face-to-face option is not crucial.

Severe hyperphosphatasemia and severe acute respiratory syndrome coronavirus 2 infection in children.

: It is now known that SARS-CoV-2 infection because of coronavirus is highly contagious and caused varying degrees of illness throughout the world. Hepatic dysfunction and the slight elevation of liver enzymes have been reported in cases of COVID-19 infection. Transient hyperphosphatasemia is a benign condition characterized by the elevation of serum alkaline phosphatase and the return to normal levels within weeks or months of first observation. We reported the first infant case of severe hyperphosphatasemia because of SARS-CoV-2 infection, in a 9-month-old child admitted to the Pediatric Covid-19 Unit of Amiens University Hospital. Given the hepatic tropism and COVID-19-related hyperinflammatory reactions, our case suggests that, an isolated severe hyperphosphatasemia in children with SARS-CoV-2 infection should increase the possibility of transient hyperphosphatasemia, even if is also demonstrated a classic natural history of the transient hyperphosphatasemia during viral infection, especially in SARS-CoV-2 infection.