STUDY THE RELATION BETWEEN THYROID FUNCTION AND RENAL FUNCTION IN CHRONIC KIDNEY DISEASE AND THE EFFECT OF DIALYSIS IN THESE PATIENTS

The aim of this work : Is to study the relation between thyroid function and renal function in chronic kidney disease and the effect of dialysis in these patients. Materials method: were categorized into three control participants, group II Chronic kidneydisease non dialysis patient and group III Chronic kidney disease(CKD) with Last twogroups arefurther subdivided into three subgroups: a) b) hypothyroid and hyperthyroid. Urine was collected for and samples were analyzed for serum creatinine, serum serum Total Tri-iodithyronine (T3), Thyroxin (T4), serum Thyroid Stimulating Hormone (TSH) and urine albumin. Glomerular filtration rate (GFR) will be measured as creatinine clearance Progression of CKD is associated with having a number of complications, including thyroid dysfunction, kidney and thyroid function and dysfunction are interrelated (2) Epidemiologic data show that CKD patients have a substantially higher prevalence of hypothyroidism compared to their non-CKD counterparts (3) Limited information is available on the relationship between thyroid hormone levels and CKD (2) .The mechanistic link and associations between kidney and thyroid disease have not been fully elucidated (4) No data to date are available about the relationships of thyroid hormone and GFR, and albumin, in CKD patients (5)


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Progression of CKD is associated with having a number of complications, including thyroid dysfunction, kidney and thyroid function and dysfunction are interrelated (2) Epidemiologic data show that CKD patients have a substantially higher prevalence of hypothyroidism compared to their non-CKD counterparts (3) Limited information is available on the relationship between thyroid hormone levels and CKD (2) .The mechanistic link and associations between kidney and thyroid disease have not been fully elucidated (4) No data to date are available about the relationships of thyroid hormone and GFR, and albumin, in CKD patients (5) The aim of the work: Is to study the relation between thyroid function and renal function in chronic kidney disease and the effect of dialysis in these patients.

Patients and Methods:-
60 participants of both sexes ranging between 19-64years,they were divided into three main groups: Gp I: control group:10healthy participants Gp II: (25 patients) chronic kidneydiseasenon dialysis patient were further subdivided into 3 subgroups: GpIIa10 Patients with normal thyroid functions,GpII b 10 Patients with hypothyroid disorder. GpII c 5 patient with hyperthyroid disorder Group III: (25 patients) Chronic kidney disease with hemodialysis three times weekly. They were further subdivided into three subgroups. GpIIIa 10 Patients with normal thyroid functions, GpIII b10 Patients with hypothyroid disorder,GpIII c 5 patient with hyperthyroid disorder. All participants were subjected to complete history taking and thorough clinical examination.Signs and symptoms of thyroid dysfunction were evaluated (6 ,7) .

Inclusion Criteria:
The presence of albuminuria for 3 or more months Exclusion Criteria: Patients were younger than 18 years and older than 65, women who were pregnant.Patient clinically diagnosed not less than 3 months,subjects who were receiving concurrent treatment with drugs that could affect thyroid function (lithium, amiodarone, iodine, methimazole, or propylthiouracil), or steroids, or contraceptive pills or other medications containing hormones, such as androgens and oestrogens, Patients with urinary infection or acute kidney injury.
From all participants urine was collected for 24 hours. To measure Urinary albumin concentration according to the method describe byBaureJD (8) Serum creatinine, will be measured by colorimetric method based on the Jafféreaction.Jaffe' colorimetric Procedure (9) Serum urea, by Berthelot Enzymatic colorimetric Procedure (10), Serum Total Tri-iodithyronine (T3), Thyroxin (T4) Serum Thyroid Stimulating Hormone (TSH) concentration by ELISA from Sigma-Aldrich (11) ,were measured , GFR will be measured as creatinine clearance (12) Statistical Analysis: Collected data were statistically analyzed by SPSS software, version 23.0, using one-way ANOVA, followed by Tukey test. Also, Pearson's correlation analysis was performed. Statistical significance was considered at p-value ≤ 0.05, for all statistical tests.  In CKD patients without and with dialysis TSH is significantly increased in hypothyroid and significantly reduced in hyperthyroidism and unchanged in Euothyroid patients as compared to control. The opposite will be observedfor T3 and T4 with exception of increase T4 in hypothyroid patients without dialysis as compared to Euothyroid patients. As regard GFR it is significantly reduced in all group studied comparedto control. In hyperthyroid patients it is significantly increased compared to Euothyroid and hypothyroid groups without dialysis and also compared to hypothyroid patients with dialysis. Urea, creatinine and urinary albumin are significantly increase in all groups compared to control.But CKD patients with dialysis urea level is significantly decreased in both hypothyroid and hyperthyroid patents as compared to Euothyroid patientsTable (1) and (2)

Discussion:-
The exact underlying mechanisms linking advanced CKD and thyroid dysfunction remain unclear (5) It is evident that the prevalence of hypothyroidism among both hypothyroid and euothyroid patients was increased in patients with reduced GFR, amount to 27.27 % for persons with GFR ≥ 30 mL/min to 77.32% in patients with GFR < 30 mL/min.Gupta et al reported similar results (4) It is clear that TSH is significantly increased in hypothyroid patients. without and with dialysis. One of possible mechanism for this increase impaired clearance of this hormone by the kidney (12) or it could be due to blunted response of TSH to TRH in CKD (13) Chandra et al concluded thatthe increase TSH level in CKD patients with hypothyroid may be due to resetting of central thyrostatetoward low level of thyroid hormone (14) .Or could be due to impaired sensitivity of Thyrotroph cells to negative feedback by the thyroid hormone (15) .Estrada et al reported that In chronic kidney disease there is decreased response to TRH feedback (16) . Rajagopalan et al observed that Circadian rhythm of TSH is disrupted in CKD suggesting that the nocturnal TSH surge is blunted in these patients resulting in increase TSH (17) ,also The half-life of TRH was 16 min in CRF and 6.5 min in normal indicate that the pharmacokinetic properties of TRH are impaired in CKD. The kidney might be an important catabolic organ for TRH (18) .
The inverse correlation between TSH and GFR observed in this work could another explanation to the increase TSH in these patients.Lo et al reported similar results (19) .As regard Total T3 and T4 they are significantly reduced in patients with hypothyroidism both with and without dialysis as compared to normal.As regard T4 in patient without dialysis it is significantly increase in hypothyroid compared to euothyroid group.
Results of the present work reveal significant direct correlation between the level of T3 andT4 with GFR Asvold et al reported similar results (20) .Other reasons may explain the reduction of T3 and T4, is that increase oxidative stress 99 in CKD patients. (21) ,ineffective clearance of inflammatory cytokines (22) kidney dysfunction decrease T3 can interfere with the activity of the 5′-deiodinase system resulting in decreased T3 production and may increase T4 (23) .
In addition, impaired renal handling of iodine inhibit thyroglobulin iodinations. Leading to decrease thyroid hormones (24) also rT3 concentrations are high in CKD patients due to a reduction in its renal clearance (25) .increased rT3 is accompanied by decrease thyroid hormones (26) ,also impaired renal handling of iodine inhibit thyroglobulin iodinations. Leading to decrease thyroid hormones (24) also rT3 concentrations are high in CKD patients due to a reduction in its renal clearance (25) .increased rT3 is accompanied by decrease thyroid hormones (26) .It is evident that in hypothyroid CKD withoutdialysis there is significantly decrease in GFR and Significant increase in urea, creatinine and urinary albumin compared to the normal control patients secondary to decrease kidney functions It is clear that in euothyroid patients there significant decrease in GFR ,and significant increase in urea creatinine and urinary albumin as compared to those of normal control. However the TSH, Total T3 and T4 are insignificantly different from the normal control indicating that these patients suffering from CKD have a compensated thyroid function. The prospective association between thyroid hormones and kidney function in euothyroid individuals, is largely unexplored (26) .
It is evident from the present results that the incidence of hyperthyroidism is very low in patients with chronic kidney disease. These results are previously reported by (27) Gupta et al found that hyperthyroidism is rarein CKD (3) .Also Mohamedali et al stated that Hyperthyroidism is usually not associated with CKD (22) .
From the results of the present work it is clear that in patients with hyperthyroid without and with dialysis there in significant lowering of TSH and increase total T3 and total T4 .This indicate that dialysis does not affect the thyroid indices in these patients. These results are similar to those reported by Lo et al , concluded that Among patients receiving hemodialysis thyroid indices were not significantly altered with dialysis (28) Hyperthyroidism results in increased GFR. compared to patient with all other studied groups with exception of insignificant change as compared to euothyroid patients with dialysis (29) .The significant increase in GFR in these patients could be explained by its influence on cardiovascular system and systemic hemodynamic effects increasing renal blood flow which results in intraglomerular hypertension, leading to increased filtration pressure and consequent hyperfiltration (30) It is clear from table (2) that the mean level of urea in all patients of CKD with dialysis ranging between 111.10 and 147.60 mg/ml whereas the mean level of creatinine6.10 and 7.88 mg/ml in spite of that they are on dialysis, this could be explained by marked reduction of GFR (31) Most of these patient fall in grade V CKD with very low GFR (31) The mean GFR ranges between 6.80 and 9.80 ml/min . Reduction in GFR, which in turn is associated with increased plasma creatinine concentrations (32) and urea. (33) As CKD progresses, plasma levels of both rises ( 33 ) .
Similarly with dialysis there is micro albuminurea.Increased transcapillary leaking of the plasma proteins such as albumin . Lower GFR and greater albuminuria are both associated with an increased rate of progression and are synergistic (34)

Conclusion:-
Thyroid and renal function should be carefully monitored in persons with poor renal function. Studies of exogenous thyroid treatment, including dosing and biochemical targets, in kidney disease .progression are needed .
Clinicians, including nephrologists, must consider the dangers of thyroid disease and its appropriate treatment in conjunction to treating CKD.

Recommendation:-
Further studies, are necessary to clarify the interaction between kidney disease and thyroid dysfunction. For that reason, regular screening for thyroid function tests is so important and aggressively recommended.