ABSTRACT
BACKGROUND: The aetiological spectrum of acute renal failure (ARF) has changed in developed countries. It was the purpose of the study to evaluate whether similar changes have occurred in this part of the world as well. METHODS: In a prospective study a total of 439 patients with ARF were evaluated. They had been admitted to one hospital during two successive periods, i.e. 1983-1990 and 1991-1997. RESULTS: Of 439 patients with ARF, 116 were admitted in 1983-1990 (first period) and 323 in 1991-1997 (second period). The age of presentation increased from 49.8+/-6.2 years in the first period to 58.8+/-16.4 years in the second. Medical causes were present in 259 cases (59%), surgical causes in 110 cases (25%), and obstetric causes in 70 cases (16%). The frequency of surgical cases decreased from 28.4% in the first period to 23.8% in the second period. The respective figures for obstetric cases were 18.9% and 14.8%. Mortality did not change with time (33.6% in the first and 31.0% in the second period); the overall mortality was 31.7%. The mortality was higher for surgical (45.5%) than for obstetric (27.8%) and medical ARF (24.3%). CONCLUSION: In the mid-1970s, the most common causes of ARF in Turkey were obstetric complications and septic abortion. The aetiological spectrum of ARF has changed and today medical causes predominate. ARF resulting from septic abortion has become rare, possibly because of liberalization of abortion in 1983 in Turkey.
Subject(s)
Acute Kidney Injury/etiology , Abortion, Septic/complications , Acute Kidney Injury/chemically induced , Acute Kidney Injury/mortality , Adult , Diarrhea/complications , Female , HELLP Syndrome/complications , Humans , Male , Middle Aged , Pregnancy , Pregnancy Complications , Prospective Studies , TurkeyABSTRACT
Patients with chronic renal failure develop secondary hyperparathyroidism with increased synthesis and secretion of parathyroid hormone (PTH) resulting in severe skeletal complications. In rats with secondary hyperparathyroidism due to 5/6 nephrectomy, there are increased PTH mRNA levels, and this mechanism was studied. Parathyroid glands were microdissected from control and 5/6 nephrectomy rats and analyzed for PTH mRNA and control genes, and the nuclei were used for nuclear run-on experiments. The cytosolic proteins of the parathyroids were used to study PTH mRNA protein binding by ultraviolet cross-linking and the degradation of the PTH transcript in vitro. Nuclear run-ons showed that the increase in PTH mRNA levels was posttranscriptional. Protein binding to the PTH mRNA 3'-UTR determines PTH mRNA stability and levels. Parathyroid proteins from uremic rats bound PTH mRNA similar to control rats by ultraviolet cross-linking. To determine the effect of uremia on PTH mRNA stability, an in vitro RNA degradation assay was performed with parathyroid proteins from uremic rats. When parathyroid proteins from control rats were incubated with PTH mRNA, there was transcript degradation already at 30 min, reaching 50% at 60 min and 90% at 180 min. With uremic parathyroid proteins, the PTH mRNA was not degraded at all at 120 min and was moderately decreased at 180 min. This decrease in degradation by uremic parathyroid proteins suggests a decrease in parathyroid cytosolic endonuclease activity in uremia resulting in a more stable PTH transcript. The increased PTH mRNA levels would translate into increased PTH synthesis and serum PTH levels, which would lead to metabolic bone disease in many patients with chronic renal failure.
Subject(s)
Parathyroid Hormone/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Uremia/genetics , Uremia/metabolism , 3' Untranslated Regions , 5' Untranslated Regions , Animals , Cytosol/metabolism , Hyperparathyroidism, Secondary/etiology , Hyperparathyroidism, Secondary/genetics , Hyperparathyroidism, Secondary/metabolism , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/metabolism , Male , Models, Biological , Nephrectomy , Parathyroid Glands/metabolism , Parathyroid Hormone/biosynthesis , Protein Binding , RNA Processing, Post-Transcriptional , RatsABSTRACT
Secondary hyperparathyroidism is a frequent complication of chronic renal failure resulting in severe bone disease. Secondary hyperparathyroidism is composed of increased in parathyroid hormone (PTH) synthesis and secretion due to an increase in PTH gene expression and parathyroid cell proliferation. PTH gene expression is regulated by calcium, phosphate and 1,25-dihydroxy vitamin D (1,25(OH)2D). 1,25(OH)2D3 injected to rats leads to a dramatic decrease in PTH gene transcription without any increase in serum calcium. Hypocalcemia leads to a large increase in PTH mRNA levels which is post-transcriptional. Hypophosphatemia leads to a marked decrease in PTH gene expression that is also post-transcriptional. The mechanisms of the post-transcriptional effects of calcium and phosphate on the PTH gene have shown to be due to changes in protein-RNA interactions at the PTH mRNA 3'-UTR. Hypocalcemia leads to increased binding of parathyroid cytosolic proteins to the PTH mRNA 3'-UTR and hypophosphatemia to decreased binding of these proteins to the PTH mRNA 3'-UTR. The binding of the parathyroid proteins stabilizes the PTH RNA in an in vitro degradation assay. In rats with experimental uremia due to 5/6 nephrectomy, there is an increase in PTH mRNA levels due to a decrease in degradation of the PTH RNA as determined by this assay. The characterization of the parathyroid cytosolic proteins that interact with the PTH mRNA 3'-UTR may lead to a clearer understanding of how changes in serum calcium and phosphate result in secondary hyperparathyroidism.
