Predictive role of fluctuating biochemical parameters for mortality in hemodialysis patients.

INTRODUCTION: High inflammation parameters like C-reactive protein and low albumin levels are considered as risk factors in CKD stage 5 patients. Due to dynamic changes in these parameters, there is evidence of an association between their variation and mortality in hemodialysis patients. METHODS: We retrospectively analyzed 153 patients on chronic hemodialysis. Dialysis-specific biochemical parameters were measured at three-month intervals over a 42-month period. Fluctuations were calculated as the percentage change in two subsequent measurements. RESULTS: Median age was 70 years. 41.10% of the patients died over the study period. Higher fluctuation rates in albumin and CRP were significantly associated with a higher mortality rate. Regression analysis revealed that only the fluctuations in albumin proved to be a predictive variable for the end point "death." If the fluctuation in albumin increases by 1%, the mortality risk rises by 22%. CONCLUSION: Fluctuations in albumin are of predictive importance in patients on chronic hemodialysis.

Effect of High Dose Active Vitamin D Therapy on the Development of Hypocalcemia After Subtotal Parathyroidectomy in Patients on Chronic Dialysis.

BACKGROUND: The period after parathyroidectomy (PTx) in dialysis patients is characterized by periods of severe hypocalcemia. This study aims to investigate the effect of high doses of active vitamin D immediately after PTx on the development of hypocalcemia. MATERIALS AND METHODS: We retrospectively reviewed 111 patients with secondary hyperparathyroidism receiving subtotal PTx between 2010 and 2019. A high dose group "HDG" (n = 67) receiving 12 µg alfacalcidol in combination with 8.550 mg calcium acetate per day, which was then adapted according to lab values, was compared with a low dose group "LDG" (n = 44) receiving up to 4 µg alfacalcidol per day. The laboratory values were recorded up to ten weeks postoperatively. RESULTS: The assumed drops in parathyroid hormone (PTH) and calcium were observed in both groups after PTx. We observed significantly lower calcium values in the LDG between days 4 and 18 postoperatively than in the HDG (p < 0.001). The proportion of severe hypocalcemia after PTx (total calcium <1.5 mmol/l) in the HDG was 8.5% on day 1 and 47% on day 4 in the LDG. Intravenous calcium requirements were significantly lower in the HDG (7.6%) than in the LDG (45.7%; p = 0.001). CONCLUSION: The period after PTx in dialysis patients is characterized by an expected drop in PTH and calcium within the first days. Ongoing high turnover is observed in the 2nd and 3rd week after PTx. Administering high doses of alfacalcidol combined with calcium acetate diminishes the episodes of severe hypocalcemia and the need for intravenous calcium.

Association between albuminuria and thyroid function in patients with chronic kidney disease.

PURPOSE: The relationship between proteinuria and thyroid function remains controversial in patients with chronic kidney disease (CKD). We prospectively investigated the association between kidney and thyroid function in thyroid antibody-negative patients through all CKD stages. METHODS: We enrolled 184 nondialysis patients (mean age: 63.1 ± 16.9 years) without previous thyroid disease or thyroid-specific antibodies. Kidney function was assessed by estimating the glomerular filtration rate (eGFR) classified according KDIGO (CKD G1-5). Kidney damage was assessed by albuminuria (albumin-to-creatinine ratio, ACR) and classified as mild, moderate, or severe (ACR1: <300, ACR2: 300-3000, and ACR3: 3000 mg/g). To evaluate thyroid function, TSH, T4, fT4, T3, fT3, reverse T3 (rT3), and thyroxine-binding globulin (TBG) were measured. RESULTS: rT3 concentrations correlated negatively with albuminuria (r = -0.286, p < 0.001) and were significantly lower in patients with severe albuminuria than in those with mild or moderate albuminuria (ACR3: 0.28 vs. ACR2: 0.32 vs. ACR1: 0.36 nmol/l, p < 0.001). The severity of albuminuria revealed no impact on TSH, fT4, T3, fT3, and TBG. EGFR correlated with increasing T4, fT4, T3, fT3, and TBG (T4: r = 0.289, p < 0.01; fT4: r = 0.196, p < 0.01; T3: r = 0.408, p < 0.01; fT3: r = 0.390, p < 0.01) but not with rT3. CONCLUSIONS: In thyroid antibody-negative patients presenting advanced CKD (stages 4 and 5), even severe kidney protein loss failed to influence thyroid hormone status. However, albuminuria severity correlated negatively with rT3, which was significantly lower in patients with albuminuria in the nephrotic range.

High Cardiovascular Risk Profile in Young Patients on the Kidney Transplant Waiting List.

BACKGROUND: Cardiovascular complications are the leading causes of morbidity and mortality in patients with end-stage renal disease. The risk profile very often contributes to their death while on the waiting list. Most studies have been carried out in older patients with end-stage renal disease, reflecting the general dialysis population. The aim of this study was to analyze the risk profile in young patients with advanced chronic kidney disease on the kidney transplant waiting list. METHODS: This was a retrospective, single-center study of 748 patients on the kidney transplant waiting list at the University Hospital Essen, Germany. Clinical and laboratory parameters were collected between 2015 and 2016. RESULTS: Of 748 patients (62% male), the median age was 48 years. Hypertension, coronary heart disease, and diabetes mellitus were the leading comorbidities, and their frequency rose significantly with age. Their median laboratory values did not differ significantly depending on age except for albumin. Hyperuricemia was quite common in our population with a prevalence of about 75% in women and 50% in men throughout all age groups. A total of 26.6% of the patients between 18 and 35 years of age had advanced anemia (hemoglobin < 10 g/dL), and thus they were affected most frequently. Elevated C-reactive protein serum levels were observed in 37.2% of the patients. Regarding the lipid profile, we observed that HDL cholesterol was within the normal range in only among 51.9% of men and 44.3% of women. CONCLUSIONS: Cardiovascular risk factors are quite common in our cohort and affect young patients similarly.

Chronic Kidney Disease Distinctly Affects Relationship Between Selenoprotein P Status and Serum Thyroid Hormone Parameters.

INTRODUCTION: Chronic kidney disease (CKD) impairs thyroid hormone (TH) metabolism and is associated with low serum triiodothyronine (T3) concentrations in patients with a low glomerular filtration rate (GFR). Whether this results from decreased T3 formation from thyroxine (T4) by impaired 5'-deiodinase (DIO) activity and/or enhanced degradation of T3 and increased reverse triiodothyronine (rT3) formation from T4 by elevated 5-DIO activity remains unclear. Both activating 5'- and the inactivating 5-deiodination of TH are catalyzed by three selenium (Se)-dependent DIO isoenzymes. Selenoprotein P (SePP) is the major constituent of serum selenium, and functions as Se transport protein from liver to kidney and several other organs. This study tested the hypothesis that serum SePP and TH status are associated with the degree of renal impairment in patients with CKD. PATIENTS AND METHODS: A total of 180 CKD patients (stages 1-5) and 70 chronic hemodialysis (CHD) patients undergoing hemodialysis three times per week for at least two years were prospectively investigated for clinical data, parameters of renal function, serum TH profile (thyrotropin, T4, free thyroxine [fT4], T3, free triiodothyronine (fT3), rT3, thyroxine-binding globulin [TBG]), C-reactive protein (CRP), and serum SePP. RESULTS: In CKD patients, renal function was negatively associated with SePP concentration (standardized ß = -0.17, p = 0.029); that is, SePP concentrations increased in more advanced CKD stages. In contrast, significantly lower SePP concentrations were found in patients on hemodialysis compared with CKD patients (M ± SD = 2.7 ± 0.8 mg/L vs. 3.3 ± .9 mg/L; p < 0.001). Notably, in CKD patients, the SePP concentration was negatively associated with T4 (standardized ß = -0.16, p = 0.039) and fT4 (standardized ß = -0.16, p = 0.039) concentrations, but no association was found with T3, fT3, rT3, T3/T4, rT3/T3, rT3/T4, or TBG concentrations. The SePP concentration was also negatively associated with CRP levels (standardized ß = -0.17, p = 0.029). In the CHD group, no association was detected between SePP and the investigated TH parameters. SUMMARY AND CONCLUSION: Impaired renal function is positively correlated with serum concentrations of SePP. In patients undergoing CHD treatment, SePP concentrations were significantly reduced, but the TH profile remained unaffected. These findings indicate an important contribution of kidney function on serum SePP homeostasis, and consequently on Se status.

Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer.

BACKGROUND: Calcitonin (CT) is a sensitive marker for evaluation of medullary thyroid cancer (MTC). However, CT measurement can vary with assay- and nonassay-dependent factors, and procalcitonin (PCT) measurement has been proposed for evaluating questionable increases in CT. METHODS: We tested 2 fully automated CT assays (Immulite [IL] and Liaison [LIA]) and 1 nonautomated CT assay (IRMA, Medipan) and compared these results with PCT (Brahms Kryptor). We evaluated preanalytical conditions and PCT cross-reactivity in sera of 437 patients with clinical conditions associated with hypercalcitoninemia. Additionally, we determined the true "nil" CT concentration in 60 thyroidectomized patients and defined CT cutoff concentrations for pentagastrin stimulation testing in 13 chronic kidney disease (CKD) patients and 10 MTC patients. RESULTS: Markedly decreased CT concentrations were found after storage of sera for >2 h at room temperature and >6 h at 4 °C. Cutoff concentrations for basal and stimulated CT were disease and assay dependent. Proton pump inhibitor therapy was the most frequent reason for increased CT. PCT concentrations were higher in patients with MTC than in patients with CKD without infections (P<0.001). Whereas IL and LIA demonstrated comparable analytical quality, the IRMA gave increased CT concentrations in nil sera and showed cross-reactivity with PCT in patients with concomitant bacterial infection. CONCLUSIONS: IL, LIA, and IRMA detected increased CT concentrations in non-MTC patients and discriminated MTC from CKD patients in pentagastrin tests. PCT assessment may be helpful in the diagnostic work-up of increased CT concentrations in questionable clinical circumstances.

Free androgen index is superior to total testosterone for short-term assessment of the gonadal axis after renal transplantation.

OBJECTIVE: Recent studies have assessed gonadal function in association with different immunosuppressive drugs in transplanted patients mainly relying on the measurement of total testosterone. It is the aim of this study to assess the short-term changes of the hypothalamic-pituitary-gonadal axis following renal transplantation using the free androgen index (FAI). PATIENTS AND METHODS: The sequential changes in total testosterone, sex hormone-binding globulin (SHBG), gonadotropin and prolactin concentrations were measured in 22 male patients before and after 1-3 days, and 1, 2 and 3 weeks following renal transplantation. RESULTS: Total testosterone and SHBG concentrations dropped significantly after transplantation (total testosterone: baseline: 15.2 +/- 1.6 nmol/l vs. 1 week: 7.9 +/- 0.8 nmol/l vs. 2 weeks: 9.8 +/- 0.9 nmol/l, SHBG: baseline: 29.9 +/- 3.2 nmol/l vs. 1 week: 19.9 +/- 2.1 nmol/l, 2 weeks: 18.9 +/- 2.4 nmol/l, p < 0.01). FAI decreased significantly after day 1-3 returning to values near baseline thereafter (baseline: 60 +/- 9% vs. day 1-3: 38 +/- 6%, 2 weeks: 61 +/- 7%; p < 0.01). There was a significant positive correlation between FAI and renal function. CONCLUSION: Measurement of the free androgen index is superior to total testosterone for assessment of the pituitary-gonadal axis in the first weeks after renal transplantation.

T-cell function after interleukin-2 therapy in HIV-infected patients is correlated with serum cortisol concentrations.

OBJECTIVES: To examine the effects of interleukin (IL)-2 therapy on in-vitro lymphocyte responsiveness in HIV-infected patients and to correlate these data with serum cortisol concentrations. DESIGN: German prospective study. METHODS: In adult patients (n = 32) treated with 9 x 10(6) IU/day interleukin-2, lymphocyte transformation tests (LTT), serum cortisol concentrations and CD4 T-cell counts were assessed before, during and after IL-2 therapy. RESULTS: A significant decrease in responses towards mitogens and recall antigens (P < 0.05) was observed on day 7 after starting a 4- to 5-day IL-2 therapy as compared to baseline. Serum cortisol levels increased (P < 0.0001) reaching a maximum on day 4, and were still elevated on day 7 (P < 0.005). CD4 T-cell counts significantly decreased with a minimum on day 2 before increasing 2.4-fold above baseline on day 7 (P < 0.005 each). A positive correlation (P < 0.05 each) was observed for changes in cortisol levels and in LTT mitogen and antigen reactions (both day 7 - 0), changes in cortisol levels (day 3 - 0) and CD4 cell counts on day 2, and corticotrophin releasing hormone test results and LTT antigen reactions on day 7. LTT responses, cortisol levels and CD4 T-cell counts returned to baseline on day 30. CONCLUSION: Serum cortisol concentrations are predictive of functional and numerical changes of T cells induced by IL-2 therapy.

Interleukin-2 given to asymptomatic HIV-infected individuals leads to an exaggerated response of the pituitary gland to the action of CRH.

BACKGROUND AND AIMS: Studies investigating the impact of interleukin-2 (IL-2) on the corticotroph axis have shown that IL-2 can stimulate cortisol and ACTH secretion. However, the site, the time course and the mechanisms of IL-2 stimulation of the corticotroph axis are still not known. The aim of this study was to gain insight into the mechanisms of IL-2 stimulation of the corticotroph axis. PATIENTS AND METHODS: A total of 9 x 10(6) IU/day IL-2 were given to 18 male HIV-infected patients treated with a combination of HIV antiviral drugs (usually two reverse-transcriptase inhibitors and one protease-inhibitor) over a course of 4-5 days. Seven of these 18 patients received a second course of IL-2. RESULTS: Cortisol levels increased significantly (P < 0.001) from baseline levels (427 +/- 118 nmol/l) to 746 +/- 132 nmol/l after 4 days of IL-2 therapy with a gradual decrease to baseline within 10 days after the end of therapy. ACTH showed a similar pattern rising from 5.9 +/- 1.9 pmol/l at baseline to 12.4 +/- 4.6 pmol/l on day 4 (P < 0.001). The cortisol response after CRH application (carried out at 15.00 h) was significantly more pronounced at the end of IL-2 application (CRH test B, baseline: 330 +/- 59 nmol/l, peak 774 +/- 134 nmol/l, 135% increase) when compared to pretreatment (CRH test A, baseline: 226 +/- 73 nmol/l, peak 459 +/- 103 nmol/l, 103% increase, P

Sensitive calcitonin measurement by two-site immunometric assays: implications for calcitonin screening in nodular thyroid disease.

The aim of this study was to investigate the impact of analytical aspects on the clinical usefulness of calcitonin (CT) measurement. In a retrospective analysis, CT levels measured by a polyclonal immunometric assay (Scantibodies Laboratory, CA, USA) were evaluated in various clinical situations. CT in newly diagnosed medullary thyroid cancer (MTC) (n = 20) ranged from 15.5-87130 pg/ml (median 661 pg/ml). Levels >10 pg/ml were seen in 7.3% of 314 patients with benign nodules, 48.9% of 45 patients with impaired kidney function, 97.7% of 87 patients on hemodialysis, 30.2% of 43 patients after renal transplantation, and in 71.0% of 31 patients with critical illnesses. Subgroups of patients were reevaluated by two monoclonal immunometric assays specific for mature CT. CT levels measured by the monoclonal immunometric assays were highly correlated to the polyclonal assay results in MTC patients, but were significantly different with a lower incidence of elevated levels in patients with renal disease and critical illnesses. In conclusion, highly sensitive assays with cut-off values of 10 pg/ml or below are mandatory for CT screening in nodular thyroid disease. The specificity of CT measurement in patients with renal disease and critical illnesses is higher with monoclonal assays specific for monomeric CT. These methodological aspects have to be regarded if CT measurement is used for decision making in nodular thyroid disease.