Hyporeninemic Hypoaldosteronism in Sickle Cell Disease

Yoshino, Mark T.; Amerian, Roger; Brautbar, Nachman

doi:10.1159/000182653

Cited by 11 publications

(4 citation statements)

References 7 publications

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“…Consistent with this, none of the participants in our cohort had proximal tubular defects, indicating that the participants in our cohort have no overt proximal tubular dysfunction. In contrast to a previous report (21), our results do not support the hypothesis of a hyporeninemic hypoaldosteronism as the primary process to elucidate this tubular acidosis because plasma renin and aldosterone concentrations were within the normal range for all of the participants. It was previously reported that adults with sickle cell disease without overt metabolic acidosis (i.e., with normal baseline plasma HCO 3 2 concentrations) are likely to have an impaired urinary acidification capacity after ammonium chloride infusion (9,21).…”

Section: Discussioncontrasting

confidence: 99%

“…In contrast to a previous report (21), our results do not support the hypothesis of a hyporeninemic hypoaldosteronism as the primary process to elucidate this tubular acidosis because plasma renin and aldosterone concentrations were within the normal range for all of the participants. It was previously reported that adults with sickle cell disease without overt metabolic acidosis (i.e., with normal baseline plasma HCO 3 2 concentrations) are likely to have an impaired urinary acidification capacity after ammonium chloride infusion (9,21). We confirmed this finding in our cohort by showing that, among participants with an abnormal response to the furosemide/fludrocortisone test, 69% had normal baseline plasma HCO 3 2 concentrations.…”

Section: Discussioncontrasting

confidence: 99%

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Tubular Acidification Defect in Adults with Sickle Cell Disease

Cazenave

Audard

Bertocchio

et al. 2019

CJASN

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Background and objectivesMetabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine.Design, setting, participants, & measurementsAmong 25 adults with sickle cell disease and an eGFR of ≥60 ml/min per 1.73 m2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ≥33 µEq/min at one or more of the six time points after furosemide and fludrocortisone administration.ResultsOf the participants (median [interquartile range] age of 36 [24–43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality (r2=0.34, P=0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity.ConclusionsAmong adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_12_10_CJN07830719.mp3

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Tubular Acidification Defect in Adults with Sickle Cell Disease

Cazenave

Audard

Bertocchio

et al. 2019

CJASN

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“…Etiologies for metabolic acidosis in SCD may include impaired ammonium availability, hyporeninemic hypoaldesteronism, or impaired distal tubular acidification capacity. 5,6,25,27 Consistent with the literature, we observed a higher prevalence of metabolic acidosis in patients with severe SCD genotype (21%), as well as a higher prevalence of metabolic acidosis in patients with moderate SCD genotypes (11%), compared to African Americans from NHANES (5%). Furthermore, the prevalence of metabolic acidosis increased with lower eGFR in both SCD genotype groups.…”

Section: Discussionsupporting

confidence: 88%

“…The prevalence of metabolic acidosis in patients with moderate SCD genotype is less clear. Etiologies for metabolic acidosis in SCD may include impaired ammonium availability, hyporeninemic hypoaldesteronism, or impaired distal tubular acidification capacity (5,6,25,27). Consistent with the literature, we observed a higher prevalence of metabolic acidosis in patients with severe SCD genotype (21%) and a higher prevalence of metabolic acidosis in patients with moderate SCD genotypes (11%) compared with African Americans from the NHANES (5%).…”

Section: Discussionmentioning

confidence: 99%

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease

et al. 2022

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Background: People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared to the general population and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD Methods: This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ+-thalassemia) SCD genotype, and 1,333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Results: Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared to in NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 mL/min/1.73m2, respectively) and moderate (52 and 102 mL/min/1.73m2, respectively) SCD genotypes compared with NHANES (34 and 46 mL/min/1.73m2). Conclusions: We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared to age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.

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Renal Disorders in Sickle Hemoglobinemia

Lear¹,

Rosa²

1991

Therapy of Renal Diseases and Related Disorders

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Hyporeninemic Hypoaldosteronism in Sickle Cell Disease

Cited by 11 publications

References 7 publications

Tubular Acidification Defect in Adults with Sickle Cell Disease

Tubular Acidification Defect in Adults with Sickle Cell Disease

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease

Renal Disorders in Sickle Hemoglobinemia

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