Triamterene crystalline nephropathy.

Medications can cause a tubulointerstitial insult leading to acute kidney injury through multiple mechanisms. Acute tubular injury, a dose-dependent process, occurs due to direct toxicity on tubular cells. Acute interstitial nephritis characterized by interstitial inflammation and tubulitis develops from drugs that incite an allergic reaction. Other less common mechanisms include osmotic nephrosis and crystalline nephropathy. The latter complication is rare but has been associated with several drugs, such as sulfadiazine, indinavir, methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been reported only rarely, and its histologic characteristics are not well characterized. We report 2 cases of triamterene crystalline nephropathy, one of which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy.

[Clinical strategies for prevention of drug-induced urinary calculi].

Drug-induced urinary calculi, although they account for only 1-2% of urinary calculi, deserve consideration because most of them are preventable. In the drug-containing calculi resulting from the crystallization of a certain drug and its metabolites in the urine, stone analysis can identify the responsible drug. While, in the drug-induced metabolic calculi caused by interference with calcium, oxalate and purine metabolism, careful clinical inquiry is necessary to reveal involvement of a certain drug in stone formation. Better awareness of the possible drugs with lithogenic potential and close surveillance of patients on long-term treatment with these drugs are necessary. Especially, in patients with a history of urolithiaisis, prescription of lithogenic drugs deserve careful consideration.

[Differential diagnosis of a macrocytic, hyperchromic anemia following alcohol abuse and simultaneous therapy with triamterene and cotrimoxazole]. / Differentialdiagnose einer makrozytären, hyperchromen Anämie bei Alkoholabusus und gleichzeitiger Triamteren- und Cotrimoxazoltherapie.

HISTORY AND ADMISSION FINDINGS: A 50-year-old woman was admitted to our emergency room because of progressive weakness. She collapsed the night before admission. Skin and mucosa were pale, she denied major infections or bleedings. An alcohol abuse was known for many years. Because of edema she received a therapy with triamteren, an infection of the urinary tract was treated with cotrimoxacol. INVESTIGATIONS: In addition to thrombocytopenia (50 Gpt/l) and leukocytopenia (1,51 10 (9)/l) we diagnosed a hyperchromic and macrocytic anemia (Hb 3,6 mmol/l [5,8 g/dl], Hk 0,17, MCH 2.52 fmol, 116,8 fl). Folic acid was decreased to 0.677 ng/ml, whereas levels of cobalamin, ferritin and iron were normal. Examination of bone marrow showed a hypercellular marrow with typical megaloblastic features of erythropoiesis and granulopoiesis. A systemic hematological disorder could be ruled out. The folic acid deficiency in our patient was the result of a long time alcohol abuse and a simultaneous therapy with mild folate antagonists (triamteren and cotrimoxacol). CLINICAL COURSE: The patient received folic acid (5 mg/d orally). Within one week the peripheral blood counts increased to normal, the follow up bone marrow examination showed a hyperplastic marrow with normal hematopoietic maturation. CONCLUSIONS: Folic acid deficiency can be aggravated because of simultaneous therapy with mild folate antagonists. In addition to megaloblastic anemia this can lead to thrombocytopenia and/or leukocytopenia. Therefore in patients with pancytopenia a deficiency of folic acid should be ruled out.

Exercise-induced acute renal failure associated with ibuprofen, hydrochlorothiazide, and triamterene.

Nonsteroidal anti-inflammatory drugs predispose to acute renal failure in conditions associated with decreased RBF. Such conditions include advanced age, hypertension, chronic renal insufficiency, diuretic use, and any condition decreasing effective circulating volume. Strenuous exercise also causes marked reductions in RBF. The patient discussed developed severe acute renal failure after strenuous exercise and therapeutic doses of ibuprofen and hydrochlorothiazide-triamterene. Urinalysis showed a nephritic sediment with red blood cell casts. Renal biopsy showed acute tubular necrosis and arteriolar nephrosclerosis. Although exercise-associated acute renal failure is uncommon, susceptible patients with exercise-induced renal ischemia and prostaglandin inhibition may develop this complication.

A systematic approach to macrocytosis. Sorting out the causes.

Because of the widespread use of multiparameter hematology instruments, physicians are often presented with patients who have macrocytosis with no obvious cause. Depending on the demographics of an individual practice, folate and vitamin B12 deficiencies may be relatively rare causes of macrocytosis, compared with alcoholism, liver disease, drugs, or myelodysplasia. Initial evaluation should include a carefully taken history and physical examination along with a complete hematologic profile, reticulocyte count, and peripheral blood smear. This initial evaluation should allow systematic consideration of the possible causes. Serum B12 and red cell folate determinations and other studies may then be undertaken as appropriate.

Irreversible renal failure associated with triamterene.

A 66-year-old man was admitted with acute oliguric renal failure. The patient was known to have chronic heart failure (ejection fraction 13%) and his medication included furosemide, digoxin and triamterene. Physical examination was unremarkable, and blood pressure was 170/80 mm Hg. Serum creatinine was 1,173 mumol/l. Renal ultrasound, CT scan and angiogram were normal. Despite correction of potential reversible factors and discontinuation of triamterene, renal function did not improve. Renal biopsy showed tubular obstruction with deposition of birefringent crystals and interstitial lymphocytic infiltration; the crystals emitted a blue autofluorescence at 425 nm, typical of triamterene. Renal tissue contained large amounts of triamterene (6.44 mg/g kidney at the initial biopsy and 400 micrograms/g kidney 5 months later). Triamterene has been previously reported to cause acute reversible renal failure, but to our knowledge, this is the first case of irreversible renal failure due to intratubular obstruction by triamterene crystal deposition.

[Photoallergy to Neotri and cross reaction to tenoretic--detection by systemic photoprovocation]. / Photoallergie auf Neotri mit Kreuzreaktion auf Teneretic--Nachweis durch systemische Photoprovokation.

A patient is presented who suffered for 3 years from increasing photosensitivity with chronic eczematous lesions in sun-exposed areas. He had taken one Neotri (triamterene, xipamide) tablet daily for 6 years. After discontinuation of the drug, phototesting and a photopatch test failed to reveal pathological reactions. Eczematous lesions, however, were induced in test areas upon systemic photochallenging with Neotri. One year later, after the antihypertensive medication had been changed from Adalat (nifedipine) to Teneretic (atenolol, chlortalidone) the eczematous photosensitive reaction recurred. Since both xipamide and chlortalidone have a chlorsulfamoyl-substituted aromatic ring in common, it seems that a photoallergic cross-reaction occurred.

Triamterene bladder calculus.

A case report of triamterene bladder calculus is presented. Triamterene containing antihypertensives should be used with caution in patients with predisposition to form stones.

[Drug-induced urinary lithiasis]. / Les lithiases urinaires médicamenteuses.

All urinary calculi should be thoroughly examined. Among 2 000 calculi analyzed by infra-red spectrophotometry, some were found to contain rare constituants and drugs which might be held responsible for urinary stone formation. These included glafenine, triamterene, co-trimoxazole, sulphaguanidine, allopurinol, phenazopyridine, flumequine and anti-acid powders containing aluminium, calcium and magnesium trisilicates and/or carbonates or bicarbonates. Considering that these drugs are widely used, the incidence of drug-induced urinary calculi appears to be very low.

Drug-induced acute interstitial nephritis with granulomas.

To shed more light on the immunopathogenesis of drug-induced acute interstitial nephritis, a combined histologic, immunopathologic, and ultrastructural study of renal biopsy specimens from nine patients with drug-induced renal disease was performed. None of the patients had pre-existing renal disease or evidence of sarcoidosis or tuberculosis. The principal drugs included a hydrochlorothiazide-triamterene combination (Dyazide), hydrochlorothiazide, fenoprofen, and furosemide and triamterene. Renal insufficiency developed approximately four to ten weeks after initiation of drug therapy. In all cases, withdrawal of the drug(s) with or without steroid therapy resulted in restoration of normal or near-normal renal function. Histologically, all biopsy specimens showed acute interstitial nephritis characterized by an intense but patchy mononuclear cell interstitial infiltrate consisting of lymphocytes, monocytes, and plasma cells, modest numbers of eosinophils, patchy tubular atrophy, interstitial edema, and normal glomeruli. All biopsy specimens contained interstitial (and, in two cases, perivascular) non-caseating granulomas, which were numerous in one case, moderate in four cases, and rare in the remainder. Direct immunofluorescence was negative for IgG, IgM, IgA, C1q, C4, and C3 along glomerular and tubular basement membranes. Immunoperoxidase staining for lysozyme (performed in three cases) demonstrated many positive cells in the infiltrate. In two cases in which granulomas were present in prepared sections, the epithelioid and multinucleated giant cells did not stain for lysozyme. Electron microscopy of the granulomas in two cases revealed that the epithelioid and giant cells had "secretory" features characteristic of hypersensitivity granulomas. These findings provide further evidence for the participation of cell-mediated immunity in the pathogenesis of at least some cases of drug-induced acute interstitial nephritis.

Acute interstitial nephritis associated with thiazide diuretics. Clinical and pathologic observations in three cases.

Renal failure insidiously developed in three patients treated with a combination of hydrochlorothiazide and triamterene five to 10 weeks after commencing therapy. All had normal renal function prior to therapy and none had preexisting renal disease. Two of the patients had eosinophilia and two had a fever. One patient was oliguric. Renal biopsy demonstrated acute interstitial nephritis histologically. Direct immunofluorescence did not disclose evidence of either immune complex or antitubular basement membrane antibody deposition. Withdrawal of the drug led to remarkable improvement with renal function returning to normal in two patients and near normal in the third. The sequence of events and the histologic findings strongly suggest that the acute interstitial nephritis was due to a drug-induced hypersensitivity reaction. Although hydrochlorothiazide appears to be the drug responsible for the reaction, certain observations suggest a possible potentiating role for triamterene.