Glomerular dysfunction

Loss of albumin in the urine following glomerular dysfunction causes oedema, which is often first seen in the dependent parts of the body, for example ankles. 

Kon V, Sugiura M, InagamiT, Harvie BR, Ichikawa I, Hoover RL. Role of endothelin in cyclosporine-induced glomerular dysfunction. Kidney Int 1990 37 1487-1491. 

Yoshioka T, Ichikawa 1. Glomerular dysfunction induced by polymorphonuclear leukocyte-derived reactive oxygen species. Am J Physiol 1989 257 F53-F59-... 

KOYA, D., LEE, I. K., ISHB, H., KANOH, H. KING, G. L. 1997. Prevention of glomerular dysfunction in diabetic rats by treatment with d-alpha-tocopherol. J Am Soc Nephrol, 8, 426-35. 

Roels HA, Lauwerys R, Materne D, Buchet JP (1975) Study on cadmium proteinuria glomerular dysfunction, an early sign of renal impairment In Proceedings of the International Symposium on Recent Advances in the Assessment of the Health Effects of Environmental Pollution (Paris, 1974) Commission of the European Communities, Luxembourg, Vol. 2, pp. 631-641... 

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

The presence of protein in the urine is a marker of glomerular and tubular dysfunction and is recognized as an independent risk factor for the progression of CKD.8 Furthermore, the degree of proteinuria correlates with the risk for progression of CKD. An increase of 1 g of protein excretion per day is associated with a five-fold increase in the risk of progression of CKD, regardless of the cause of CKD.9 The mechanisms by which proteinuria potentiates CKD are discussed later. Microalbuminuria is also linked with vascular injury and increased cardiovascular mortality.10... 

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

The risk of renal dysfunction caused by drugs increases with the normal decline in glomerular filtration rate that occurs in old age... 

Kroll RB, Robinson GD, Chung JH. 1994b. Characterization of trihalomethane (THM)-induced renal dysfunction in the rat. I Effects of THM on glomerular filtration and renal concentrating ability. Arch Environ Contam Toxicol 27(1) 1-4. 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

Extensive literature has accumulated concerning other forms of renal dysfunction during long-term lithium therapy, including chronic interstitial nephritis and minimal-change glomerulopathy with nephrotic syndrome. Some instances of decreased glomerular filtration rate have been encountered but no instances of marked azotemia or renal failure. 

Oral bioavailability of adefovir dipivoxil is about 59% and is unaffected by meals it is rapidly and completely hydrolyzed to the parent compound by intestinal and blood esterases. Protein binding is low (< 5%). The intracellular half-life of the diphosphate is prolonged, ranging from 5 to 18 hours in various cells this makes once-daily dosing feasible. Adefovir is excreted by a combination of glomerular filtration and active tubular secretion and reguires dose adjustment for renal dysfunction however, it may be administered to patients with decompensated liver disease. 

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