Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-five children (34 boys, 21 girls; age range, 1 day to 18 years) with increased echogenicity of the renal medullary pyramids at ultrasound evaluation were identified. The clinical diagnoses associated with hyperechoic medullary pyramids could be separated based on the presence or absence of hypercalciuria. Patients with drug-induced hypercalciuria included 10 infants treated with furosemide, two treated with long-term steroid therapy, and one treated with excessive amounts of vitamin D. Other clinical conditions associated with hypercalciuria included renal tubular acidosis (n = 10), Bartter syndrome (n = 5), hyperparathyroidism (n = 3), Williams syndrome (n = 2) and medullary sponge kidney (n = 2). Ten children with transient renal insufficiency and three with sickle cell disease had normal urine calcium concentration. Isolated disease entities accounted for the remainder of cases. A specific diagnosis can usually be made in a patient with hyperechoic renal medullary pyramids by using a systematic clinical approach that includes evaluation of patient age, serum and urine calcium concentration, and renal function.
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PMID:Hyperechoic renal medullary pyramids in infants and children. 188 61

Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment of underlying disease, correction of electrolyte imbalance, particularly hypokalemia and hyperkalemia, and most importantly, the use of alkali. This will prevent or reduce all the various complications.
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PMID:Renal tubular acidosis. 208 16

Of 240 adults with sickle cell anemia seen over 11 years, 12 had the nephrotic syndrome. In 9 (75%) the glomerular lesion, sickle glomerulopathy, consisted of mesangial expansion and basement membrane duplication. Six patients had type IV renal tubular acidosis. Four of the 9 Patients died within 24 months (17 +/- 5; mean +/- SD), while 5 survived 36 months or longer (80 +/- 49); no significant differences were seen between the former and the latter in age, admission serum creatinine and C3 levels, urinary protein excretion, or the frequency of renal tubular acidosis. Chronic azotemia developed in 3 and acute renal shutdown in another 2. Of 22 patients with sickle glomerulopathy (our 9 added to 13 from the literature) 11 died within 2 years. Ten of these (91%) had developed renal failure, compared to only 5 of the 11 (45%) who survived longer than 2 years (p less than 0.05). The 5-year mortality in the general population of sickle cell anemia is 3.75%, and 75% of patients aged 15 years or older survive 18 years or longer. The nephrotic syndrome, most often caused by sickle glomerulopathy, occurs in 4% of patients with sickle cell anemia, leading to renal failure in two-thirds and death in 2 years in half the patients. The development of chronic azotemia correlates strongly with early mortality. The prognosis is much worse than that in the general population of sickle cell anemia.
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PMID:Prognosis of the nephrotic syndrome in sickle glomerulopathy. A retrospective study. 360 31

Patients with sickle cell nephropathy have been shown to have a distal type of incomplete renal tubular acidosis. We evaluated renal tubular acidification before and after indomethacin administration because prostaglandins have been shown to inhibit the transepithelial potential difference in the collecting tubule and since we previously found indirect evidence of increased prostaglandin synthesis in patients with sickle cell nephropathy. Indomethacin did not change urine pH in the sickle cell anemia (SCA) patients or in the control subjects. It induced, however, an increase in titratable acid excretion particularly in the SCA patients. Ammonium excretion decreased after indomethacin in the SCA patients while it did not change significantly in the control subjects. In the SCA patients, net acid excretion did not rise after indomethacin. In contrast there was an increase in net acid excretion after indomethacin administration in the control subjects. We conclude from our study that the inability of patients with SCA to lower urine pH to a normal extent after ammonium chloride loading is not improved by indomethacin. The decrease in ammonium excretion after indomethacin administration in SCA might be due to an effect of the prostaglandin synthesis inhibitor indomethacin on ammoniagenesis.
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PMID:The influence of indomethacin on renal acidification in normal subjects and in patients with sickle cell anemia. 685 Dec 66

This report describes the occurrence of hyperkalemic hyperchloremic metabolic acidosis in six patients with sickle cell hemoglobinopathies. Three patients had sickle cell anemia, two had sickle cell trait and one had S-C disease. In all patients, decreased renal potassium excretion was demonstrated by the finding of a fractional potassium excretion lower than that of control subjects with comparable glomerular filtration rates. Two patterns of impaired urinary acidification were discerned. Four patients had a urinary pH above 5.5 in the presence of systemic acidosis and, thus, were classified a having distal renal tubular acidosis. The remaining two patients had very low rates of ammonium excretion despite intact capacity to lower urinary pH below 5.5 during systemic acidosis; this pattern was ascribed to selective aldosterone deficiency. Sickle cell hemoglobinopathies should be included in the differential diagnosis of hyperkalemic hyperchloremic metabolic acidosis.
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PMID:Hyperkalemic hyperchloremic metabolic acidosis in sickle cell hemoglobinopathies. 703 25

A patient with the acquired immunodeficiency syndrome (AIDS) and sickle cell anemia presented to the University of Wisconsin Hospital on two separate occasions with pneumocystis carinii pneumonia (PCP). On both occasions he was treated with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). Several days into each treatment course he developed hyperkalemia and systemic acidosis consistent with hyperkalemic renal tubular acidosis (RTA). The abnormalities resolved in the first instance with the addition of amphotericin B while continuing TMP/SMX, and in the second upon discontinuation of the TMP/SMX. While an increasing number of cases with TMP/SMX-induced hyperkalemia have been reported, hyperkalemic RTA is an uncommon complication of TMP/SMX therapy, occurring in patients with predisposing factors for acidosis such as aldosterone defects, medullary dysfunction and renal insufficiency.
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PMID:Hyperkalemic renal tubular acidosis induced by trimethoprim/sulfamethoxazole in an AIDS patient. 977 24

Band 3 proteins, members of the anion exchange family of proteins (AE 0-3), are involved in a number of physiological activities such as cell volume and osmotic homeostasis, HCO3-/Cl- exchange, red cell aging, IgG binding and cellular removal, and the maintenance of the structural integrity of cells. They are present in the membranes of all cells and cellular organelles examined including Golgi, mitochondria and nuclei. The first polymorphisms of band 3 discovered were the asymptomatic band 3 Memphis variants carrying the Lys --> Gly substitution at position 56 in the cytoplasmic tail, and band 3 Texas (high transport band 3 Texas) with a mutation in the critical transmembrane, anion transport domain (Pro --> Leu substitution at position 868). The rate at which band 3 mutations were discovered accelerated in the mid 1990s and there are now over 50 known. The most common polymorphisms of band 3 are the Diego blood group antigens which reside on extracellular loops of the protein. Southeast Asia ovalocytosis (SAO; a nine amino acid deletion of residues 400-408) is a band 3 mutation known only in the heterozygous state in which it does not cause disease. It is thought to confer resistance to malaria by altering red cell deformability. Band 3 mutations are responsible for a subset of the heterogeneous group of disorders known as hereditary spherocytosis (HS). HS is a relatively common congenital or inherited group of anemias characterized by chronic hemolysis and abnormal red cell morphology. Red cells in the subset of HS with band 3 mutations behave like they are band 3 deficient either because the mutant protein is not incorporated into the membrane or because it is not functional. HS can be caused by mutations in any of at least 5 proteins involved in membrane stability. Band 3 mutations are associated with diseases in cells besides erythrocytes. For example, 2 types of distal renal tubular acidosis are the result of band 3 mutations either alone or combined with SAO. Band 3 alterations are implicated in neurological diseases such as familial paroxysmal dyskinesia, idiopathic generalized epilepsies, and neuro- or choreoacanthocytosis although they have not been demonstrated to be causative. Mutations in other genes can cause changes in band 3. An example is sickle cell anemia where the increased oxidation causes accelerated aging of band 3 and increased IgG binding and cellular removal.
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PMID:Band 3 and its alterations in health and disease. 1509 83

We report a rare case of two young male siblings with sickle cell anemia who presented with bilateral lower limb deformities, failure to thrive, polyuria, and polydipsia. On investigations, they were found to have normal anion gap metabolic acidosis, hypokalemia, and nephrocalcinosis were seen on ultrasonography of the kidneys. These reports were suggestive of distal renal tubular acidosis (dRTA). They were started on oral alkali replacement and potassium therapy with which clinical improvement was seen. Conventionally, renal tubular dysfunction is thought to occur infrequently in patients with sickle cell anemia. Hence, we report this rare association between sickle cell anemia and dRTA.
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PMID:Distal renal tubular acidosis in sickle cell anemia. 3015 44