It has been postulated that hyperparathyroidism in chronic renal failure results from hypocalcemia, occurring, in part, from phosphate retention and/or deficient 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] synthesis. However, many studies have failed to demonstrate hyperphosphatemia or low 1,25-(OH)2D levels in patients with mild renal failure. We measured creatinine clearance (CCr), fractional excretion of phosphorus (FEP), and serum phosphorus, ionized calcium, and plasma N-terminal PTH, and 1,25-(OH)2D concentrations in 21 normal subjects and 51 patients with renal failure. Patients with mild renal failure (Ccr, greater than 40 mL/min.1.73 m2) had normal mean serum phosphorus and ionized calcium and decreased mean 1,25-(OH)2D levels compared with those in normal subjects. In patients with moderate renal failure (CCr, 20-40), the mean ionized calcium level was normal, plasma PTH levels and FEP were elevated, and the decrement in 1,25-(OH)2D was more pronounced. The mean ionized calcium level was decreased only in the group of patients with severe renal failure (CCr, less than 20). The 1,25-(OH)2D values correlated positively with CCr and negatively with the log of plasma PTH and serum phosphorus concentrations. Log of plasma PTH correlated negatively with CCr and positively with FEP. The ionized calcium concentration correlated very weakly with CCr and the log of the plasma PTH level. These data demonstrate the presence of hyperparathyroidism, normocalcemia, and 1,25-(OH)2D deficiency in renal failure and are consistent with a role for 1,25-(OH)2D in the suppression of parathyroid activity through as yet unidentified mechanisms.

Lymphocytes have receptors for PTH and patients with chronic renal failure have high blood levels of PTH and impaired lymphocyte function. It is possible, therefore, that PTH affects lymphocyte function. We studied the interaction between PTH and proliferation of human lymphocytes in vitro and examined potential mechanisms for such an interaction. 1-84 PTH stimulated in a dose dependent manner PHA-induced proliferation of T cells but had no effect on PWM-induced proliferation. The hormone did not alter CD4/CD8 ratio. Inactivation of PTH abolished its stimulatory effect. PTH augmented IL-2 production by PHA-activated T cells but did not increase expression of IL-2R. 1-34 PTH also stimulated PHA-induced T cell proliferation. TPA augmented PHA-induced T cell proliferation but the addition of PTH to the culture stimulated by PHA and TPA did not augment further the proliferation of T cells. Staurosporin reversed the stimulation by PTH of the PHA-induced lymphocyte proliferation. Both 1-34 and 1-84 PTH stimulated cyclic AMP production by lymphocytes. Forskolin did not affect PHA-induced T cell proliferation although it stimulated cyclic AMP generation. The results show that: 1) PTH acts on T cells; 2) acute exposure to PTH augments PHA-induced T cell proliferation and IL-2 production; 3) this action of PTH is related to its biological activity and is most likely due to the ability of PTH to enhance entry of calcium into cells and/or stimulation of protein kinase C but is independent of cyclic AMP generation.

Autopsy data on 24 chronic maintenance hemodialysis patients who had received varying doses of parenteral iron as the iron-dextran complex were reviewed for evidence of iron overload (hemosiderosis) and tissue fibrosis or organ dysfunction (hemochromatosis). Hemosiderosis was frequent in patients who received high total doses of iron but absent in those who received little or no iron. The degree of tissue iron did not increase with increased iron administration above a total of 2.5 g. Hemochromatosis or organ dysfunction secondary to tissue iron deposition was not noted in any patient. Chronic parenteral iron administration may improve anemia and result in tissue iron deposition but does not lead to hemochromatosis.

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.