Kidneys chronic renal failure

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

A 30-year-old male with a two-year history of chronic renal failure requiring dialysis consents to transplantation. A donor kidney becomes available. He is given cyclosporine to prevent transplant rejection just before surgery What is the most likely adverse effect of this drug ... 

Chronic renal failure is a common consequence of diabetes but this case is complicated by the loss of fluid and electrolytes (sodium and potassium) due to diarrhoea and vomiting. Normally, the kidneys would respond to such a challenge and maintain homeostasis but Mrs Amin s kidneys were unable to do so. Mrs Amin was put on haemodialysis and treated to control the diabetes. 

However, in patients with renal failure there is a strange and currently unexplained observation in relation to non-renal clearance. If this is measured for some compounds it also is found to be depressed even though it is the kidney that is diseased and not the liver The picture becomes a little clearer if the same non-renal (presumed hepatic) clearance is measured again in patients after renal dialysis when the hepatic clearance has been found to have risen to control values. Recent animal experiments have demonstrated that the circulating inhibitor of hepatic cytochrome P450 may be parathyroid hormone. Parathyroidectomy of rats with chronic renal failure prevented the reduction in liver cytochrome activity (see Michaud et al., 2006). 

Erythropoietin is a protein produced mainly in the cortex of the kidney. Erythropoietin binds to a receptor on the surface of erythroid precursor cells. It stimulates erythropoiesis and is primarily indicated for the treatment of anemia in patients with chronic renal failure. Other indications are the management of anemia in cancer patients and in HIV positive subjects treated with anti-HIV regimens. 

Diazoxide lowers blood pressure within 3 to 5 minutes after rapid intravenous injection, and its duration of action may be 4 to 12 hours. Interestingly, if diazoxide is either injected slowly or infused its hypotensive action is quite modest. This is believed to be due to a rapid and extensive binding of the drug to plasma proteins. Both the liver and kidney contribute to its metabolism and excretion. The plasma half-life is therefore prolonged in patients with chronic renal failure. 

Suki WN. Use of diuretics in chronic renal failure. Kidney Int 1997 51 S33-S35. 

D) He had glomerulonephritis at age 24 and developed chronic renal failure but received a kidney transplant 10 years ago. 

Clinical pharmacology Erythropoietin is instrumental in the production of red cells from the erythroid tissues in the bone marrow. The majority of this hormone is produced in the kidney in response to hypoxia, with an additional 10% to 15% of synthesis occurring in the hver. Erythropoietin functions as a growth factor, stimulating the mitotic activity of the erythroid progenitor cells and early precursor cells. Chronic renal failure patients often manifest the sequelae of renal dysfunction, including anemia. Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. 

Calcium and phosphate enter the body from the intestine. The average American diet provides 600-1000 mg of calcium per day, of which approximately 100-250 mg is absorbed. This figure represents net absorption, because both absorption (principally in the duodenum and upper jejunum) and secretion (principally in the ileum) occur. The amount of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of absorption (principally in the jejunum) is greater, ranging from 70% to 90%, depending on intake. In the steady state, renal excretion of calcium and phosphate balances intestinal absorption. In general, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidney. The movement of calcium and phosphate across the intestinal and renal epithelia is closely regulated. Intrinsic disease of the intestine (eg, nontropical sprue) or kidney (eg, chronic renal failure) disrupts bone mineral homeostasis. 

Haffner D, Nissel R, Wuhl E, Schaefer F, Bettendorf M, Tonshoff B, Mehls O. Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. 

Calcifediol (25[OH]D3) may also be used to advantage. Calcifediol is less effective than calcitriol in stimulating intestinal calcium transport, so that hypercalcemia is less of a problem with calcifediol. Like dihydrotachysterol, calcifediol requires several weeks to restore normocalcemia in hypocalcemic individuals with chronic renal failure. Presumably because of the reduced ability of the diseased kidney to metabolize calcifediol to more active metabolites, high doses (50-100 Pg daily) must be given to achieve the supraphysiologic serum levels required for therapeutic effectiveness. 

Fig. 11. Cluster analysis used to assist in diagnosis of kidney diseases (adapted from Batchelor 418>). (A) acute nephritis, (B) nephrotic syndrome, (C) normal, (D) acute renal infection, (E) essential hypertension, and (F) chronic renal failure...

Cowley et al. (1996) described the Han SRPD rat strain which develops autosomal dominant polycystic kidney disease with chronic renal failure that resembles human autosomal dominant polycystic kidney disease. 

Stockelman et al. (1998) described chronic renal failure in a mouse model of human adenine phospho-ribo-syltransferase deficiency. Hamilton and Cotes (1994) used a partial nephrectomy model in mice with two-thirds of the total renal mass excised to evaluate erythropoiesis and erythropoietin production from extrarenal sources such as the submandibulary salivary gland. Koumegawa et al. (1991) suggested the DBA/2FG-pcy mouse, which develops numerous cysts in kidney cortex and medulla, a progressive anemia and an elevation of blood urea nitrogen, as a useful spontaneous model of progressive renal failure. 

Fine et al. (1990), Vaneerdeweg et al. (1992) described surgical techniques for kidney resection to produce chronic renal failure in dogs. 

Ali SM, Laping NJ, Fredrickson TA et al. (1998) Angiotensinconverting enzyme inhibition attenuates proteinuria and renal TGFpimRNA expression in rats with chronic renal disease. Pharmacology 57 20-27 Ashab I, Peer G, Blum M et al. (1995) Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production. Kidney Int 47 1515-1521 Bardoux P, Martin H, Ahoulay M et al. (1999) Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus Study in vasopressin-deficient Brattleboro rats. Proc Natl Acad Sci USA 96 10397-10402... 

Kakinuma Y, Kawamura T, Bills T et al. (1992) Blood pressure-independent effect of angiotensin inhibition on vascular lesions of chronic renal failure. Kidney Int 42 46-55 Kimura M, Suzuki T, Hishida A (1999) A rat model of progressive renal failure produced by microembolism. Am J Pathol 155 1371-1380... 

Poux JM, Lartigue M, Chaisemartin RA et al. (1995) Uraemia is necessary for erythropoietin-induced hypertension in rats. Clin Exp Pharmacol Physiol 22 769-771 Roczniak A, Fryer JN, Levine DZ, Burns KD (1999) Downregulation of neuronal nitric oxide synthase in the rat remnant kidney. J Am Soc Nephrol 10 704-713 Santos F, Chan JCM, Hanna JDetal. (1992) The effect of growth hormone on the growth failure of chronic renal failure. Pe-diatr Nephrol 6 262-266... 

Vaziri ND, Oveisi F, Ding Y (1998) Role of increased oxygen free radical activity in the pathogenesis of uremic hypertension. Kidney Int 53 1748-1754 Wolf SC, Brehm Br, Gaschler F et al. (1999) Protective effects of endothelin antagonists in chronic renal failure. Nephrol Dial Transplant 14, Suppl 4 29-30 Wong NLM, Wong EEC (1991) Increased release of atrial natriuretic peptide by the atria of rats with experimental renal failure. Nephron 57 89-93... 

From the symptoms and examination of blood and urine, a diagnosis of chronic renal failure is made. Unfortunately, considerable kidney damage can occur, often over a period of years, before the patient notices the symptoms associated with chronic renal failure. As the amount of functioning kidney tissue decreases, blood electrolytes begin to change. At the same time, the ability of the kidney to excrete nitrogenous waste decreases and urea concentration in the blood rises (uraemia). The patient may remain symptom-free until the concentration of urea rises sufficiently to cause the nausea and vomiting Kevin has recently experienced. 

Q6 The cause of excessive PTH secretion maybe primary, secondary, or tertiary. In primary hyperparathyroidism one or more glands show exaggerated functions, do not respond to the normal feedback via serum calcium and secrete PTH autonomously. However, the most common cause (80% of the cases) is a benign tumour of parathyroid tissue in one of the glands. Secondary hyperparathyroidism is due to the development of hypocalcaemia. There is an increase in the level of PTH however, the kidneys, which are major target organs for this hormone, fail to respond and therefore the level of calcium remains low. In tertiary hyperparathyroidism, which occurs in chronic renal failure, the hyperplastic parathyroid cells lose their sensitivity to circulating calcium levels. This leads to autonomous secretion of PTH. 

Steinman MA, Steinman TI. Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1996 27(l) 143-6. 

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