The Calcium/Phosphorus Homeostasis in Chronic Kidney Disease: From Clinical Epidemiology to Pathophysiology

Abstract

RESUMOIntrodução: O propósito do presente trabalho consistiu em descrever alguns dos mecanismos fisiopatológicos envolvidos nas perturbações do metabolismo fosfo-cálcico na doença renal crónica a partir de um processo simples de filtragem de dados e de alguns conceitos básicos de teoria de sistemas. Material e Métodos: Foram estudados os valores (um conjunto por doente, obtido numa única colheita de sangue) de creatinina, cál-cio, fósforo, paratormona, 25-hidroxivitamina D e 1,25-dihidroxivitamina D num grupo de 2507 doentes com doença renal crónica não sujeitos a substituição renal. As variáveis foram emparelhadas e tratadas, primeiro por um processo de média deslizante e depois por distribuição por classes de frequência. Os resultados obtidos foram interpretados à luz do conceito de ansa de retro-controlo contendo dois ramos de sinais opostos cuja intersecção define o 'ponto operacional' do sistema. Este ponto desloca-se ao longo da evolução da doença e o sentido do deslocamento indica qual dos dois fatores (a calcémia ou a concentração de paratormona, por exemplo) está a afetar primariamente o sistema. Resultados: Esta análise mostrou que a evolução das relações entre as variáveis observadas seguiu um padrão monótono, bifásico ou trifásico. Discussão: À medida que a doença renal crónica progride ocorrem alterações na regulação do metabolismo fosfo-cálcico, passando por diferentes fases. Numa fase mais avançada há uma perda do controlo das glândulas paratiróides pela calcémia e pela fosfatémia. A sensibilidade à ação inibitória da 1,25-dihidroxivitamina D diminui progressivamente mas nunca desaparece. Conclusão: A metodologia utilizada na análise de uma base de dados clínicos permitiu ilustrar mecanismos fisiopatológicos subjacentes. Palavras-chave: Cálcio; Fósforo; Hiperparatiroidismo; Homeostase; Insuficiência Renal Crónica ABSTRACT Introduction: A simple data filtering process together with some basic concepts of control theory applied to electronically stored clinical data were used to identify some of the pathophysiological mechanisms underlying the perturbations of the calcium/phosphorus homeostasis in chronic kidney disease. Material and Methods:Retrospective data (a set per patient of serum single value concentrations of creatinine, calcium, phosphorus, parathormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) from 2507 patients with stable chronic kidney disease not on renal replacement therapy were studied. The variables were paired and subjected sequentially to a moving average and partioned into frequency classes. The plots were interpreted using the concept of a feedback loop comprising two branches of opposite sign and of set point of the loop. The set point for each pair of variables is displaced in the course of the disease and this displacement indicates which of the two factors involved (the serum concentrations of calcium or parathormone, for example) is primarily affected.Results: This analysis showed that in the course of the development of chronic kidney disease the relationships bet...

Habitual Intakes, Food Sources and Excretions of Phosphorus and Calcium in Three German Study Collectives

“…However, kidney diseases are often characterized by an impaired glomerular filtration rate (GFR). In the first stages of CKD the phosphorus homeostasis (especially the phosphate concentration in plasma) is maintained by PTH and FGF23, but when GFR continues to fall (GFR < 50 mL/min) compensatory mechanisms fail leading to hyperphosphatemia [ 33 , 34 ]. Hyperphosphatemia is strongly associated with increased cardiovascular morbidity and mortality in healthy subjects and in patients with CKD [ 10 , 35 ].…”

Calcium and Phosphate Metabolism, Blood Lipids and Intestinal Sterols in Human Intervention Studies Using Different Sources of Phosphate as Supplements—Pooled Results and Literature Search

“…Kidney diseases are characterized by an impaired glomerular filtration rate and in the first stages of chronic kidney disease (CKD) the phosphate concentration in plasma is maintained by PTH and FGF23. But, when glomerular filtration rate continues to fall (<50 mL/min), compensatory mechanisms fail and this leads to hyperphosphatemia [ 53 , 54 ]. Hyperphosphatemia is strongly associated with increased cardiovascular morbidity and mortality in patients with CKD [ 55 ].…”

Severe Hypocalcemia in a Patient with Tuberous Sclerosis Complex

“…Nevertheless, the possibility of combined hypothyroidism remains due to the severely decreased serum calcium level17). The recently aggravated renal function could have contributed to hypocalcemia with hyperphosphatemia, but the presence of severe hypocalcemia could not be fully attributed to CKD progression alone18). In addition, the unidentified herbal medicine, poor nutritional status, and reduced sunlight exposure could act as causal factors.…”