Alteration of renal function in hyperthyroidism: Increased tubular secretion of creatinine and decreased distal tubule delivery of chloride

doi:10.1016/0026-0495(92)90075-L

Metabolism

Volume 41, Issue 4, April 1992, Pages 402-405

https://doi.org/10.1016/0026-0495(92)90075-L Get rights and content

Abstract

In 77 untreated patients (16 males and 61 females, aged 12 to 65 years) with hyperthyroid Graves' disease, and in 107 control subjects (36 males and 71 females, aged 13 to 78 years), blood urea nitrogen (BUN), serum creatinine (Scr) levels, and BUN to Scr ratios ( $BUN Scr$ ) were determined. In 53 patients, the determinations were performed before treatment and after restoration of euthyroidism by treatment with an antithyroid drug. In addition, in seven untreated patients and seven normal subjects, renal clearances of creatinine (C_cr), urea nitrogen (C_un), inulin (C_in), and p-aminohippurate (C_PAH) were also determined. The distal tubule delivery of chloride (DTD) and the distal fractional chloride reabsorption (DFCR) were also measured in these subjects: $DTD = (C_{H2O} + C_{cl}) C_{in} × 100$ , and $DFCR = C_{H2O} (C_{H2O + C_{cl})} × 100$ , where C_H2O and C_cl stand for clearances of H₂O and chloride, respectively. BUN was significantly elevated, while Scr was significantly depressed, in untreated patients with hyperthyroid Graves' disease. Accordingly, the $BUN Scr$ was markedly elevated. Restoration of euthyroidism accompanied the normalization of all these abnormalities. C_cr and C_un were significantly elevated, but C_in (glomerular filtration rate [GFR]) was slightly, but insignificantly, elevated in the patients. As a result, the ratios $C_{cr} C_{in}$ and $C_{un} C_{in}$ were significantly greater in the patients than in controls ( $C_{cr} C_{in}, 1.42 v 1.00; C_{un} C_{in}, 0.92 v 0.68$ ). The amounts of urinary creatinine and urea nitrogen (UN) excretion were decreased and increased, respectively, and DTD was significantly depressed, but DFCR was unchanged in the patients. We conclude that BUN is elevated, Scr is depressed, and the $BUN Scr$ is increased in hyperthyroidism. The increase in BUN is due to increased production, whereas the decrease in Scr is due to decreased production and increased renal clearance. A high $C_{cr} C_{in}$ suggests that there is additional creatinine excretion occurring besides that produced by glomerular filtration. DTD is reduced in hyperthyroidism; this fact well explains the seemingly paradoxical increase of plasma renin activity in the presence of an increased GFR reported in this disorder.

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Assisting the diagnosis of Graves' hyperthyroidism with pattern recognition methods and a set of three routine tests parameters, and their correlations with free T4 levels: Extension to male patients
2011, Biomedicine and Pharmacotherapy
Citation Excerpt :
When we tried different combinations of parameters, the use of γ-GTP, and AST, ALT often erroneously placed patients with hepatic disease into the hyperthyroid zone, whereas ALP, S-Cr, and TC gave the best screening results as was found for female cases. As for the set of two parameters (ALP and TC) recommended in the guidelines for Graves’ disease [21,22] both the classification ability of learning samples and the screening ability of the test samples were worse than the results for the set of three parameters, which indicates the importance of S-Cre [23]. Fig. 2 shows a SOM that was constructed using the three best routine tests (ALP, S-Cr, and TC) as training samples, and 133 test samples (black or white) from patients who had undergone routine tests at the Department of Comprehensive Medicine of Tohoku University Hospital after complaining of illness, have been projected onto it.
In our previous paper, we proposed a novel screening method that aids the diagnosis of female patients with Graves’ hyperthyroidism via two types of neural networks and the use of routine test data. This method can be applied by non-specialists during physical checkups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists; i.e., to improve patients’ QOL. In this report, we investigate whether the screening method is also applicable to males since sex differences exist in routine test data. The values of 14 routine test parameters for 78 subjects with definite diagnoses (31 patients with Graves’ hyperthyroidism and 48 healthy volunteers) were adopted as training data, and 133 individuals who had also undergone the same routine tests at Tohoku University Hospital were screened for Graves’ hyperthyroidism using our method. The present examination of our screening method in males showed its high screening ability with the set of parameters used (low serum creatinine, elevated alkaline phosphatase, and low total cholesterol). It was also found that there is strong multiple correlation between a set of three parameters and serum free thyroxine (FT4) in male patients with Graves’ hyperthyroidism. A formula for FT4 consisting of three parameters was obtained, and this can be utilized in place of the true FT4 value. This result also supports the usefulness of our screening method.
Cystatin C as a Biomarker in Kidney Disease
2011, Biomarkers of Kidney Disease
Presently, 12 human proteins are known to contain polypeptide chains with sequences homologous to that of cystatin C and form the human cystatin protein superfamily of cysteine protease inhibitors. Cystatin C is the strongest human inhibitor of important cysteine proteases such as cathepsin K and H and is, in contrast to the other cystatins, present in significant concentrations in all investigated human body fluids. The structures of the cystatin C gene, comprising three exons and two introns, and of its promoter, indicate that the gene is a so-called housekeeping gene suggesting a stable rate of production of the protein in all nucleated cell types. As a low molecular mass protein (13.4 kDa) cystatin C is mainly catabolised by free filtration in the glomeruli followed by virtually complete tubular reabsorption. Although GFR is a good general indicator of renal disease, it will not detect renal diseases in which the composition of the glomerular filtrate is deranged in the presence of a normal GFR. Studies using gold standard determinations of GFR are still required to unequivocally demonstrate that cystatin C has an advantage over measured GFR as a predictor of cardiovascular events. Although a raised level of cystatin C might indicate a decline in GFR due to significant atherosclerosis in the renal arteries and thus an increased probability of simultaneous significant atherosclerosis in other vital arteries, e.g. the coronary and brain arteries, other mechanisms explaining the usefulness of cystatin C as a predictor of aging success might be involved.
Assisting the diagnosis of Graves' hyperthyroidism with Bayesian-type and SOM-type neural networks by making use of a set of three routine tests and their correlation with free T4
2010, Biomedicine and Pharmacotherapy
In our previous paper, we proposed a novel screening method that assists the diagnosis of Graves’ hyperthyroidism via two types of neural networks by making use of routine test data. This method can be applied by non-specialists during physical check-ups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists, that is, to improve patients’ QOL. In this report, the amount of female sample data was increased and routine test data (14 parameters) from 120 subjects with a known diagnosis (35 patients with Graves’ hyperthyroidism and 85 healthy volunteers) were adopted as training data, before 171 individuals who had also undergone the same routine tests at the Tohoku University Hospital were screened by the network for Graves’ hyperthyroidism. The present re-examination of the screening method showed its high screening ability with the set of parameters used (low serum creatinine was added to the established measures of elevated alkaline phosphatase and low total cholesterol that appear in the Graves’ hyperthyroidism guidelines) and robustness due to the increase of the training sample data. It was also found that there is a strong correlation between the three parameters and serum free thyroxine (FT4) in Graves’ hyperthyroidism, which supports the usefulness of our screening method.
Interactions between thyroid and kidney function in pathological conditions of these organ systems: A review
2009, General and Comparative Endocrinology
Citation Excerpt :
The intrarenal feedback mechanism increases the GFR to cope with the threatening hypoperfusion and the escape of urine entering the distal tubule, which has to be replaced by the delivery of proximal tubule fluid (Straub, 1977). Thyroid hormones increase mRNA expression of chloride channels (ClC) in a dose-dependent way (Shirota et al., 1992; Santos et al., 2003) and also increase the activity of ClC and Cl absorption in the proximal tubule and Henle’s loop. Tubulo-glomerular feedback adjusts GFR after a decreased chloride load is sensed within the distal tubule by the macula densa (Graves et al., 1994).
Thyroidal status affects kidney function already in the embryonic stage. Thyroid hormones influence general tissue growth as well as tubular functions, electrolyte handling and neural input. Hyper- and hypo-functioning of the thyroid influences mature kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, electrolyte pumps, the secretory and absorptive capacity of the tubuli, and the structure of the kidney.
Hyperthyroidism accelerates several physiologic processes, a fact which is reflected in the decreased systemic vascular resistance, increased cardiac output (CO), increased renal blood flow (RBF), hypertrophic and hyperplastic tubuli, and increased glomerular filtration rate (GFR). Renal failure can progress due to glomerulosclerosis, proteinuria and oxidative stress.
Hypothyroidism has a more negative influence on kidney function. Peripheral vascular resistance is increased with intrarenal vasoconstriction, and CO is decreased, causing decreased RBF. The influence on the different tubular functions is modest, although the transport capacity is below normal. The GFR is decreased up to 40% in hypothyroid humans. Despite the negative influences on glomerular and tubular kidney function, a hypothyroid state has been described as beneficial in kidney disease.
Kidney disease is associated with decreased thyroid hormone concentrations caused by central effects and by changes in peripheral hormone metabolism and thyroid hormone binding proteins. Geriatric cats form an animal model of disease because both hyperthyroidism and chronic kidney disease (CKD) have high prevalence among them, and the link between thyroid and kidney affects the evaluation of clinical wellbeing and the possible treatment options.
Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine
2009, Domestic Animal Endocrinology
Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR.
Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine (¹³¹I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n = 16) and group B (impaired kidney function, n = 5).
Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P < 0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P < 0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P < 0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG.
Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia.
Hyperthyroidism and the kidney
2006, Clinical Techniques in Small Animal Practice
Hyperthyroidism and chronic renal failure (CRF) are both common diseases of older cats. Hyperthyroidism increases GFR by a variety of physiologic effects. Chronic renal failure can suppress total T4 concentrations in cats with concurrent hyperthyroidism, and free T4 is not a useful distinguishing test. Medical therapy (ie, methimazole) is recommended in cats with pre-existing CRF. Overt renal failure occurs in approximately 30% of cats treated for hyperthyroidism. It usually occurs within one month of treatment and tends to remain mild and stable over time. There is no practical way to predict which cats will develop CRF after treatment of hyperthyroidism, although GFR measurement does seem useful.

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Alteration of renal function in hyperthyroidism: Increased tubular secretion of creatinine and decreased distal tubule delivery of chloride

Abstract

Kidney Int

Am J Med

Am J Med

J Biol Chem

An elevation of BUN/creatinine ratio in patients with hyperthyroidism

Horm Metab Res

Plasma natriuretic peptide, plasma renin activity and aldosterone during treatment of hyperthyroidism due to Graves' disease

Horm Metab Res

Renal function and electrolyte levels in hyperthyroidism: Urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes

Clin Endocrinol

A hypothesis for the thyroid hormone-induced increase in RPF and GFR

Nephron

Kidney function in various thyroid states

J Clin Endocrinol Metab