A Case of Hypokalemia Caused by Left Native Renal Artery Stenosis in a Kidney Transplant Recipient.

A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor kidney transplantation from her husband. After the kidney transplantation, her serum creatinine level remained around 0.7 mg/dL, but her serum potassium level remained low at around 3.5 mEq/L despite potassium supplementation and spironolactone. The patient's plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly elevated (20 ng/mL/h and 868 pg/mL, respectively). A CT angiogram of the abdomen performed 1 year previously suggested stenosis of the left native renal artery, which was considered responsible for the hypokalemia. Renal venous sampling was done on both the native kidneys and the transplanted kidney. Since renin secretion from the left native kidney was significantly elevated, a laparoscopic left nephrectomy was performed. Postoperatively, the renin-angiotensin-aldosterone system was markedly improved (PRA: 6.4 ng/mL/h, PAC: 147.3 pg/mL), and the serum potassium levels also improved. Pathological examination of the removed kidney showed many atubular glomeruli and hyperplasia of the juxtaglomerular apparatus (JGA) in residual glomeruli. In addition, renin staining showed strong positivity in the JGA of these glomeruli. Here, we report a case of hypokalemia caused by left native renal artery stenosis in a kidney transplant recipient. This valuable case study provides histological confirmation of maintained renin secretion in an abandoned native kidney after kidney transplantation.

Unilateral renal artery stenosis presenting as acute flaccid paralysis: a rare presentation.

Renovascular hypertension is one of the common causes of secondary hypertension. Here we report a case of patient of renal artery stenosis presenting to the emergency department as a case of acute flaccid paralysis. Renal artery stenosis has been associated with hypokalaemia, but rarely reported to be symptomatic. Initial correction of hypokalaemia leads to improvement of weakness and aetiological work up for hypokalaemia with hypertension revealed hypokalaemia due to hyperaldosteronism secondary to unilateral renal artery stenosis. The patient was managed medically with aldosterone antagonist in the anti hypertensive therapy and weakness did not recur despite withdrawal of potassium supplements. On follow-up, the patient was ambulatory with no signs of weakness, controlled blood pressure and normal potassium level.

Paradigm Shifts in Atherosclerotic Renovascular Disease: Where Are We Now?

Results of recent clinical trials and experimental studies indicate that whereas atherosclerotic renovascular disease can accelerate both systemic hypertension and tissue injury in the poststenotic kidney, restoring vessel patency alone is insufficient to recover kidney function for most subjects. Kidney injury in atherosclerotic renovascular disease reflects complex interactions among vascular rarefication, oxidative stress injury, and recruitment of inflammatory cellular elements that ultimately produce fibrosis. Classic paradigms for simply restoring blood flow are shifting to implementation of therapy targeting mitochondria and cell-based functions to allow regeneration of vascular, glomerular, and tubular structures sufficient to recover, or at least stabilize, renal function. These developments offer exciting possibilities of repair and regeneration of kidney tissue that may limit progressive CKD in atherosclerotic renovascular disease and may apply to other conditions in which inflammatory injury is a major common pathway.

Long-term safety and efficacy of renin-angiotensin blockade in atherosclerotic renal artery stenosis.

PURPOSE: The activation of the renin-angiotensin-aldosterone system caused by renal ischaemia in atherosclerotic renal artery stenosis (ARAS) may be responsible for serious cardiovascular and renal consequences. The aim of the study was to assess the long-term safety, tolerability and outcomes of the use of angiotensin I-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients with ARAS. METHODS: Thirty-six patients with angiographically defined ARAS (managed either with revascularization or only with medical treatment) were prospectively assessed for the safety, tolerability and outcomes of the use of ACEis or ARBs. RESULTS: The mean period of follow-up was 88.9 ± 37.8 months. A statistically significant reduction in systolic and diastolic blood pressure was recorded over time (P < 0.001). While estimated glomerular filtration rate remained almost stable during the study period (0.816), nuclear EDTA-GFR showed a significant reduction over time (P = 0.03). Mean time from diagnosis/intervention to end-stage renal disease for the cohort of 36 patients was 165.38 ± 13.62 months. Mean overall patient survival was 135.36 ± 15.25 months, with fourteen deaths (38.8%) occurring during the observational period. ACEi/ARB therapy was discontinued transiently in only 4 subjects. CONCLUSIONS: The use of ACEis/ARBs is safe and effective in patients with ARAS independently of any parameters.

Treatment of resistant hypertension.

AIM: Resistant hypertension (RH) is a common clinical problem. Patients with RH have increased cardiovascular risk. These patients also have high risk for having reversible causes of hypertension and may potentially benefit from special diagnostic or therapeutic considerations. The purpose of this review was to discuss RH, its definition, recognition, evaluation and treatment. METHODS: Authors define RH and the implications of this definition. They present latest data on its prevalence, prognostic implications, genetics, and patient characteristics. Elements of pseudoresistance and possible etiologies of treatment resistance are also identified. Lastly, diagnostic and therapeutic approaches to RH are discussed, focusing on antihypertensive medication classes that have proven benefit in patients with RH, and also on novel therapeutic approaches in these patients. CONCLUSION: RH is a common clinical problem and carries an increased risk for cardiovascular morbidity and mortality, as well as target organ damage. Patients with RH are aat high risk for reversible causes of hypertension and may benefit from special diagnostic or therapeutic considerations. Elements of pseudoresistance, intake of interfering substances and secondary causes of hypertension should be searched for and corrected, if possible. Therapeutic lifestyle modifications should be emphasized. Medical therapy includes optimizing diuretic use and considering the use of mineralocorticoid antagonists as add on antihypertensive agents. Novel approaches include surgical and transcatheter techniques, chronotherapy, and new classes of antihypertensive agents.

Arteritis de Takayasu: caso clínico y seguimiento por 23 años / Takayasu arteritis: case-report and outcome in 23 years

La arteritis de Takayasu es una vasculitis granulomatosa, rara en pediatría, que afecta a la arteria aorta y grandes vasos, produciendo hipertensión arterial y alteración de los pulsos. Nuestro objetivo es presentar a una paciente diagnosticada a los 5 meses de edad y analizar los aspectos clínicos, de diagnóstico, tratamiento y seguimiento de esta enfermedad. Caso Clínico: Paciente de 23 años de edad sexo femenino, cuyo diagnóstico de Arteritis de Takayasu fue hecho en la época de lactante, encontrando en ella hipertensión arterial severa, diferencia de presiones en extremidades superiores, y estenosis de aorta y arterias renales. Se muestra la evolución desde el punto de vista clínico y de imágenes, destacando la importancia actual de la angio resonancia para el control de las estenosis arteriales y de la ecografía para el control de crecimiento renal. Se discute, de acuerdo a la literatura al alcance, respecto al modo de seguimiento de la actividad de la enfermedad, especialmente en relación al hemograma y velocidad de eritrosedimentación. Se analiza el tratamiento con esteroides y otros inmunosupresores, como Azatioprina y Metotrexato, así como el tiempo a usar estos medicamentos y las indicaciones, cuando corresponde, de cirugía y/o angioplastía percutánea. Conclusión: Aunque se trata de una patología poco frecuente, hay que considerarla en los niños hipertensos severos; es importante tomar las presiones en las 4 extremidades, así como los pulsos, y si es necesario debe realizarse el estudio angiográfico, el cual actualmente es posible realizarlo en forma no invasiva con Angio-Resonancia y/o Angio-TAC, con buenos resultados. El tratamiento médico, fundamentalmente con corticoides, es efectivo en la mayoría de los casos y la cirugía debe reservarse a aquellos casos en que exista riesgo de oclusión de alguna de las grandes arterias.

Antioxidant intervention blunts renal injury in experimental renovascular disease.

Atherosclerotic renovascular disease (RVD) amplifies damage in a stenotic kidney by inducing pro-inflammatory mechanisms and disrupting tissue remodeling. Oxidative stress is increased in RVD, but its direct contribution to renal injury has not been fully established. The authors hypothesized that chronic antioxidant intervention in RVD would improve renal function and attenuate tissue injury. Single-kidney hemodynamics and function at baseline and during vasoactive challenge were quantified using electron-beam computed tomography in pigs after 12 wk of experimental RVD (simulated by concurrent hypercholesterolemia and renal artery stenosis, n = 7), RVD daily supplemented with antioxidant vitamins C (1 g), and E (100 IU/kg) (RVD+Vitamins, n = 7), or controls (normal, n = 7). Renal tissue was studied ex vivo using Western blot analysis and immunohistochemistry. Basal renal blood flow (RBF) and glomerular filtration rate (GFR) were similarly decreased in the stenotic kidney of both RVD groups. RBF and GFR response to acetylcholine was blunted in RVD, but significantly improved in RVD+Vitamins (P < 0.05 versus RVD). RVD+Vitamins also showed increased renal expression of endothelial nitric oxide synthase (eNOS) and decreased expression of NAD(P)H-oxidase, nitrotyrosine, inducible-NOS, and NF-kappaB, suggesting decreased superoxide abundance and inflammation. Furthermore, decreased expression of pro-fibrotic factors in RVD+Vitamins was accompanied by augmented expression of extracellular (matrix metalloproteinase-2) and intracellular (ubiquitin) protein degradation systems, resulting in significantly attenuated glomerulosclerosis and renal fibrosis. In conclusion, chronic antioxidant intervention in early experimental RVD improved renal functional responses, enhanced tissue remodeling, and decreased structural injury. This study supports critical pathogenic contribution of increased oxidative stress to renal injury and scarring in RVD and suggests a role for antioxidant strategies in preserving the atherosclerotic and ischemic kidney.

Hypercholesterolemia and hypertension have synergistic deleterious effects on coronary endothelial function.

OBJECTIVE: Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function. METHODS AND RESULTS: Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity. CONCLUSIONS: These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.

Homocysteine and atheromatous renal artery stenosis.

Hyperhomocysteinemia is an independent risk factor for vascular disease, frequently observed in patients with severe renal impairment. Hyperhomocysteinemia has never been considered as a possible risk factor in renal artery stenosis. We investigated plasma folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine beta-synthase (CBS) 844ins68 polymorphisms, and homocysteine levels before and after methionine (100 mg/kg) loading in 58 patients with angiographically documented renal artery stenosis and mildly impaired renal function. One hundred and two normotensive subjects with angiographically normal coronary arteries and no history or clinical or angiographic evidence of atherosclerosis in other vascular districts, were considered as a control group. Mean total homocysteine levels were significantly higher in patients than in controls (P<0.01), as was the prevalence of hyperhomocysteinemia (51.7% vs. 32.3%, P<0.05). However, MTHFR alleles and genotypes as well as CBS 844ins68 mutation frequencies were similar in the two groups, whereas a lower folate level was observed in the patients. Moreover, patients with MTHFR A/A genotype showed a poorer folate status than control subjects, suggesting that a subclinical folate deficiency may be very frequent in renal artery stenosis, regardless of C677T mutation. In conclusions, hyperhomocysteinemia is common in patients with atheromatous renal artery stenosis; a subclinical folate deficiency seems to be involved, regardless of MTHFR thermolabile or CBS insertion genotypes. Folate supplementation might be useful in the management of overall vascular risk of these patients.

Hypertension and renal artery stenosis: a complex clinical scenario.

Hypertension remains the most common reason for patients to visit physicians in the United States. Although awareness of hypertension among patients continues to increase, adequate control of hypertension remains poor. In addition, as the population of patients with hypertension ages, atherosclerosis becomes increasingly prevalent. Atherosclerotic renal artery stenosis is the most common secondary cause of hypertension and can cause hypertension to be difficult to control. Atherosclerotic renal artery stenosis may also result in chronic renal insufficiency. The physician must be aware of the clinical scenarios in which renal artery stenosis may occur, methods of diagnosis, and indications for intervention.

Estenosis de la arteria renal y embarazo / Stenosis of the renal artery and pregnancy

La hipertensión renovascular es una entidad de diagnóstico infrecuente en el embarazo y agrega un factor de riesgo grave para la madre y el feto. El manejo médico conservador es una de las alternativas terapéuticas en esta etapa y las opciones quirúrgicas (revascularización, angioplastia endoluminal percutánea y nefrectomía) se reservan para casos severos en que el tratamiento no es satisfactorio, habiendo en la literatura actual casos resueltos en forma invasiva durante la gestación. Presentamos un caso de hipertensión renovascular en una gestante joven, que fue manejado en forma conservadora

Glomerular alterations in experimental oliguric and nonoliguric acute renal failure.

Studies were performed in oliguric and nonoliguric forms of uranyl acetate (UA)-induced and ischemic acute renal failure (ARF) to examine whether a reduction in GFR is correlated with glomerular morphologic alterations. UA-induced nonoliguric and oliguric ARF were induced in rabbits by i.v. injections of 0.9 and 2 mg/kg, respectively. A 60-min renal artery clamping produced nonoliguric ARF in previously uninephrectomized rats, but oliguric ARF in the clamped kidneys of sham-nephrectomized animals. A decline in the whole-kidney CIn rate was more marked in oliguric ARF kidneys of both models than in nonoliguric ARF kidneys. Also, tubular damage was more pronounced in oliguric kidneys when compared with nonoliguric kidneys. Scanning electron microscopic observations revealed glomerular alterations in oliguric and nonoliguric kidneys in both models, evidenced by a flattening and spreading of podocyte cell bodies associated with loss of epithelial foot processes and a reduction in the density and diameter of endothelial fenestrae. There was no significant difference in these glomerular changes between oliguric and nonoliguric kidneys. The findings suggest that less reduction in the whole-kidney GFR in nonoliguric ARF kidneys is ascribed largely to less pronounced tubular damage rather than to less severe glomerular morphologic alterations.

Evaluation of the efficacy of felodipine in two models of acute renal failure in dogs.

Acute renal failure was induced in pentobarbital anesthetized dogs either by withdrawal of the blood and/or by acute renal artery occlusion and efficacy of felodipine in preserving renal function was evaluated. In Wiggers' model of hemorrhagic shock, animals were allowed to bleed into a reservoir and after maintaining a hypotensive state (40-45 mm Hg) for 150 minutes, blood was reinfused and recovery in the renal function was evaluated. In a separate series, a renal artery was completely occluded for 45 minutes and after release of the occlusion recoveries in various markers of renal function were monitored. Felodipine 0.01 mumol/kg i.v. or the vehicle was administered ten minutes before hemorrhage or ten minutes prior to initiation of renal artery occlusion. Comparison of the data between the vehicle-treated dogs from the two models show that although renal blood flow (RBF) was restored to similar levels, recoveries in glomerular filtration rate (GFR), urine volume (UV), urinary excretion of sodium (UNa V) and potassium (UK V) were severely depressed in shock model (15 to 25% of the basal value) and consistently lower than the recoveries in the renal artery occlusion model (30-50%). These data could suggest that the extent of renal impairment is more severe in hemorrhagic shock. Nevertheless, felodipine pretreatment provided significant protection to renal function from ischemic damage in both the models; the drug-treated groups were characterized by significant recoveries in GFR, UNa V and UK V (60-100%) and by prompt and full restoration of RBF and UV.(ABSTRACT TRUNCATED AT 250 WORDS)

[Symptomatology and treatment of neonatal hypertension]. / Symptomatologie en behandeling van neonatale hypertensie.

A newborn child of a diabetic mother is described, who developed neonatal hypertension after birth. Clinical signs were not specific and the diagnosis would have been missed if blood pressure had not been measured. The cause of the neonatal hypertension appeared to be a thrombus in the left renal artery, probably originating from the ductus arteriosus Botalli. Control of the neonatal hypertension according to a stepwise treatment regime was very difficult. Based on our experience and on study of the literature it is advised to start treatment in the acute stage with nifedipine orally or with sodium nitroprusside intravenously.

Effect of calcium entry blocker nitrendipine on renal function after renal vascular occlusion.

The ability of the Ca entry blocker nitrendipine to improve postischemic renal function was studied in nine groups (n = 70) of rats. After anesthesia, nitrendipine was administered for 15 min through the femoral vein. The dose administered depended on the group. Group 1 (n = 7), the control, received only 0.9% NaCl, group 2 (n = 12) 0.25 mg/kg; group 3 (n = 10) 0.50 mg/kg; group 4 (n = 8) 0.75 mg/kg; group 5 (n = 6) 1.00 mg/kg; group 6 (n = 7) 1.50 mg/kg; group 7 (n = 7) 2.00 mg/kg; group 8 (n = 6) 2.50 mg/kg; and group 9 (n = 7) 3.00 mg/kg. After the administration of nitrendipine, the kidneys were rendered ischemic for one hour by cross-clamping the renal vessels. Comparison of 24-h creatinine clearances for 72 h after reversal of ischemia demonstrated that nitrendipine was capable of providing a degree of protection against renal ischemia and the protective effect was dose dependent (p less than .05).

[Arterial hypertension with hypokalemia]. / Ipertensione arteriosa con ipopotassiemia.

After a careful review of the literature on physiopathological role of the renin-angiotensin-aldosterone system in cases of arterial hypertension with hypokalaemia, a simple diagnostic procedure is suggested to differentiate between this and secondary hypertensions which, though few, are often curable. Three clinical cases examined in the medical department of Casalpusterlengo Hospital are presented in which the study of the renin-angiotensin system proved decisive for a correct diagnosis of the hypertension.