Poliuria post-obstructiva. Análisis fisiopatológico de un caso / Post-obstructive polyuria. Pathophysiological analysis of a case

The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

[Post-obstructive polyuria. Pathophysiological analysis of a case]. / Poliuria post-obstructiva. Análisis fisiopatológico de un caso.

The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

[Decision making among older adults in hemodialysis. A qualitative assessment]. / Toma de decisiones en hemodiálisis crónica: estudio cualitativo en adultos mayores.

BACKGROUND: In Chile there are 22,310 people in Chronic Hemodialysis (CHD), 53% of them older adults (OA). Shared decision-making and advance directives (AD) are especially important in OA with end-stage chronic renal failure, since they have greater levels of disability, morbidity and mortality, raising doubts about the benefit of therapy. AIMS: To understand the experience in decision making and explore ways to express AD, in OA in CHD. MATERIAL AND METHODS: A qualitative phenomenological study, performing 12 in-depth interviews to OA who had been at CHD for at least one year. RESULTS: The analysis revealed four broad comprehensive categories, two related to participation in the decision to enter CHD, namely the experience of subjects as spectators and their lack of interest for decision support and two referred to the expression of AD, namely the difficulty in facing their own finitude and resistance to express AD. CONCLUSIONS: There is little participation of older adults in the decision about their admission to dialysis therapy, and once they enter the CHD program they are not prepared to discuss AD in general, nor an eventual suspension of dialysis in particular.

Toma de decisiones en hemodiálisis crónica: estudio cualitativo en adultos mayores / Decision making among older adults in hemodialysis. A qualitative assessment

Background: In Chile there are 22,310 people in Chronic Hemodialysis (CHD), 53% of them older adults (OA). Shared decision-making and advance directives (AD) are especially important in OA with end-stage chronic renal failure, since they have greater levels of disability, morbidity and mortality, raising doubts about the benefit of therapy. Aims: To understand the experience in decision making and explore ways to express AD, in OA in CHD. Material and Methods: A qualitative phenomenological study, performing 12 in-depth interviews to OA who had been at CHD for at least one year. Results: The analysis revealed four broad comprehensive categories, two related to participation in the decision to enter CHD, namely the experience of subjects as spectators and their lack of interest for decision support and two referred to the expression of AD, namely the difficulty in facing their own finitude and resistance to express AD. Conclusions: There is little participation of older adults in the decision about their admission to dialysis therapy, and once they enter the CHD program they are not prepared to discuss AD in general, nor an eventual suspension of dialysis in particular.

Intoxicación por etilenglicol, fisiopatología y enfrentamiento clínico / Ethylene glycol poisonin: an update

Toxic alcohols can produce severe poisoning with multiple organic involvement and even death. The most common form is ethylene glycol. The diagnosis can be extremely difficult if there is no history of its consumption. Its clinical presentation can simulate other conditions. Ethylene glycol poisoning is characterized by an initial rise in plasma osmolal gap that decreases during the evolution, while alcohol is metabolized to acids. This last condition causes a metabolic acidosis with elevated anion gap. The clinical manifestations are diffuse neurological involvement initially, followed by hemodynamic alterations due to myocardial damage associated with hypocalcemia and acidemia. Subsequently, severe tubular renal damage appears, which may require renal replacement therapy, and finally, focal neurological alterations. To treat this poisoning, it is necessary to inhibit the transformation of alcohol into acids, increase the metabolism of the latter or withdraw them directly with hemodialysis.

Intoxicación por etilenglicol, fisiopatología y enfrentamiento clínico.

Toxic alcohols can produce severe poisoning with multiple organic involvement and even death. The most common form is ethylene glycol. The diagnosis can be extremely difficult if there is no history of its consumption. Its clinical presentation can simulate other conditions. Ethylene glycol poisoning is characterized by an initial rise in plasma osmolal gap that decreases during the evolution, while alcohol is metabolized to acids. This last condition causes a metabolic acidosis with elevated anion gap. The clinical manifestations are diffuse neurological involvement initially, followed by hemodynamic alterations due to myocardial damage associated with hypocalcemia and acidemia. Subsequently, severe tubular renal damage appears, which may require renal replacement therapy, and finally, focal neurological alterations. To treat this poisoning, it is necessary to inhibit the transformation of alcohol into acids, increase the metabolism of the latter or withdraw them directly with hemodialysis.

[Conflicts of interest in nephrology]. / Conflictos de intereses en nefrología.

Since doctors disposed of effective tools to serve their patients, they had to worry about the proper management of available resources and how to deal with the relationship with the industry that provides such resources. In this relation-ship, health professionals may be involved in conflicts of interest that they need to acknowledge and learn how to handle. This article discusses the conflicts of interest in nephrology. Its objectives are to identify those areas where such conflicts could occur; to help to solve them, always considering the best interest of patients; and to help health workers to keep in mind that they have to preserve their autonomy and professional integrity. Conflicts of interest of professionals in the renal area and related scientific societies, with the industry producing equipment, supplies and drugs are reviewed. Dichotomy, payment for referral, self-referral of patients and incentives for cost control are analyzed. Finally, recommendations to help preserve a good practice in nephrology are made.

Conflictos de intereses en nefrología / Conflicts of interest in nephrology

Since doctors disposed of effective tools to serve their patients, they had to worry about the proper management of available resources and how to deal with the relationship with the industry that provides such resources. In this relation­ship, health professionals may be involved in conflicts of interest that they need to acknowledge and learn how to handle. This article discusses the conflicts of interest in nephrology. Its objectives are to identify those areas where such conflicts could occur; to help to solve them, always considering the best interest of patients; and to help health workers to keep in mind that they have to preserve their autonomy and professional integrity. Conflicts of interest of professionals in the renal area and related scientific societies, with the industry producing equipment, supplies and drugs are reviewed. Dichotomy, payment for referral, self-referral of patients and incentives for cost control are analyzed. Finally, recommendations to help preserve a good practice in nephrology are made.

[Ethical issues perceived by health care professionals working in chronic hemodialysis centers]. / Problemas ético-clínicos en hemodiálisis crónica: percepción de médicos y enfermeras.

BACKGROUND: Clinical teams working at chronic hemodialysis centers (CHC) frequently have to face ethical problems, but there is no systematic approach to deal with them. AIM: To study the ethical problems perceived by health professionals at CHC. MATERIAL AND METHODS: Eighty randomly selected physicians and 139 nurses from 23 CHC, answered a structured questionnaire, devised by the research team. RESULTS: Twenty-six percent of respondents had postgraduate studies in clinical ethics. The ethical problems mentioned by respondents were therapeutic disproportion in 66.7%, lack of communication between patients, their families and the clinical team in 25.9%, personal conflicts of interests related with hemodialysis prescription in 14.6% and conflicts of interests of other members of the clinical team in 30.6%. The percentage of respondents that experienced not starting or discontinuing hemodialysis treatment due to decision of patients’ relatives was 86.8%. Only 45.2% of health professionals had the opportunity to take part in decision-making meetings. Eighty seven percent of respondents supported the use of advanced directives in the event of a cardio respiratory arrest during treatment. CONCLUSIONS: To improve the approach to ethical problems in CHC, it is necessary to improve training in clinical ethics, promote an effective dialogue between the patients, their families and health professionals, and follow their advance directives in case of cardiac arrest during treatment.

Problemas ético-clínicos en hemodiálisis crónica: percepción de médicos y enfermeras / Ethical issues perceived by health care professionals working in chronic hemodialysis centers

Background: Clinical teams working at chronic hemodialysis centers (CHC) frequently have to face ethical problems, but there is no systematic approach to deal with them. Aim: To study the ethical problems perceived by health professionals at CHC. Material and Methods: Eighty randomly selected physicians and 139 nurses from 23 CHC, answered a structured questionnaire, devised by the research team. Results: Twenty-six percent of respondents had postgraduate studies in clinical ethics. The ethical problems mentioned by respondents were therapeutic disproportion in 66.7%, lack of communication between patients, their families and the clinical team in 25.9%, personal conflicts of interests related with hemodialysis prescription in 14.6% and conflicts of interests of other members of the clinical team in 30.6%. The percentage of respondents that experienced not starting or discontinuing hemodialysis treatment due to decision of patients’ relatives was 86.8%. Only 45.2% of health professionals had the opportunity to take part in decision-making meetings. Eighty seven percent of respondents supported the use of advanced directives in the event of a cardio respiratory arrest during treatment. Conclusions: To improve the approach to ethical problems in CHC, it is necessary to improve training in clinical ethics, promote an effective dialogue between the patients, their families and health professionals, and follow their advance directives in case of cardiac arrest during treatment.

[Recommendations of the Ethics Committee of the Chilean Society of Nephrology for the management of ethical problems in adult end stage renal disease patients]. / Recomendaciones del Comité de Ética de la Sociedad Chilena de Nefrología para el manejo de los problemas ético-clínicos de pacientes adultos con enfermedad renal crónica terminal.

There are different approaches to treat patients with End Stage Renal Disease (ESRD): hemodialysis, peritoneal dialysis, renal transplantation and conservative medical management. The choice of the best therapy for each patient, needs both clinical and ethical skills. The Ethics Committee of the Chilean Society of Nephrology has elaborated recommendations to help health workers to deal with the ethical and clinical problems related to patients suffering ESRD. Its goal is to guide, at a national level, the effective use of minimal standards in the treatment and care of patients with ESRD, including appropriate care and information for patients, therapy selection, management of difficult cases and potential conflicts.

Recomendaciones del Comité de Ética de la Sociedad Chilena de Nefrología para el manejo de los problemas ético-clínicos de pacientes adultos con enfermedad renal crónica terminal / Recommendations of the Ethics Committee of the Chilean Society of Nephrology for the management of ethical problems in adult end stage renal disease patients

There are different approaches to treat patients with End Stage Renal Disease (ESRD): hemodialysis, peritoneal dialysis, renal transplantation and conservative medical management. The choice of the best therapy for each patient, needs both clinical and ethical skills. The Ethics Committee of the Chilean Society of Nephrology has elaborated recommendations to help health workers to deal with the ethical and clinical problems related to patients suffering ESRD. Its goal is to guide, at a national level, the effective use of minimal standards in the treatment and care of patients with ESRD, including appropriate care and information for patients, therapy selection, management of difficult cases and potential conflicts.

Expression of gremlin, a bone morphogenetic protein antagonist,is associated with vascular calcification in uraemia.

BACKGROUND: Vascular calcification has been widely recognized as a significant contributor to cardiovascular risk in patients with chronic kidney disease. Recent evidence suggests that BMP-7 decreases the vascular calcification observed in uraemic rats, while BMP-2 could also be participating in this process. Gremlin, a bone morphogenetic protein antagonist, has been detected in rat aortic vascular smooth muscle cells (VSMCs), and since the role of the VSMCs into vascular calcification in uraemia is considered critical in this process, we hypothesized that gremlin could be participating in its pathogenesis. With this aim, we studied its expression in aorta from uraemic rats with calcitriol-induced vascular calcification and in 16-vessel biopsies of uraemic patients undergoing kidney transplantation. METHODS: Gremlin was detected by in situ hybridization (ISH) and immunohistochemistry (IMH). BMP-7, BMP-2 and BMP-2 receptor (BMPR2) were detected by IMH. Vascular calcification was assessed by the von Kossa staining method. Sham-operated and 5/6 nephrectomized rats (NFX) (1.2%P) were treated with vehicle or calcitriol (80 ng/kg, intraperitoneally every other day). Rats were killed after 4 weeks of treatment, and abdominal aorta was dissected for assessment of gremlin expression and vascular calcification. Epigastric arteries were obtained from dialysis patients during kidney transplantation procedure. Arteries from kidney donors were also studied. RESULTS: NFX rats developed a mild vascular calcification, whereas NFX-calcitriol rats developed a severe vascular and tissue calcification. A marked overexpression of gremlin was observed in the vascular media of aorta from NFX-calcitriol rats as compared with NFX and sham-calcitriol groups (4.8 +/- 1.3 versus 0.59 +/- 0.17 versus 0.19 +/- 0.07 percentage/mm(2), P < 0.01), and correlated with the BMP-2 and BMPR2 expression. Sham rats showed minimal or null gremlin expression. BMP-7 was not found in sham or calcified arteries. In human studies, we observed strong expression of gremlin mRNA and protein in the media layer of vessels from uraemic patients as compared with those from normal humans (staining score 3.72 +/- 0.95 versus 0.91 +/- 0.08 percentage/mm(2), P < 0.05). CONCLUSION: We observed a marked gremlin overexpression in the media layer of vessels in uraemic rats and patients in association with vascular calcification and BMP-2 expression. We postulate that gremlin may play a role in the vascular calcification process in uraemia, and its interaction with BMP-7 or BMP-2 remains to be elucidated.

Hipokalemia, hipovolemia y repercusión electrocardiográfica secundarias a ingesta prolongada de furosemida: Caso clínico / Hypokalemia, hypovolemia and electrocardiographic changes due to furosemide abuse: Report of one case

Hypokalemia (serum K+ < 3.5 mEq/1) is a potentially serious adverse effect of diuretic ingestión. We report a 27 year-old woman admitted with muscle weakness, a serum potassium of 2.0 mEq/1, metabolic alkalosis and EKG abnormalities simulating cardiac ischemia, that reverted with potassium chloride administration. She admitted high dose furosemide self-medication for edema. Glomerular filtration rate, tubular sodium reabsortion, potassium secretion, the renin-aldosterone system, total body water distribution and capillary permeability, were studied sequentially until 90 days after her admission. There was hyperactivity of the renin-aldosterone axis, reduction in extracellular and intracellular volumes, normal capillary permeability and high sodium tubular reabsorption, probably explained by a "rebound" salt retention associated with her decreased extracellular volume.

[Hypokalemia, hypovolemia and electrocardiographic changes due to furosemide abuse. Report of one case]. / Hipokalemia, hipovolemia y repercusión electrocardiográfica secundarias a ingesta prolongada de furosemida: Caso clínico.

Hypokalemia (serum K+ < 3.5 mEq/1) is a potentially serious adverse effect of diuretic ingestion. We report a 27 year-old woman admitted with muscle weakness, a serum potassium of 2.0 mEq/1, metabolic alkalosis and EKG abnormalities simulating cardiac ischemia, that reverted with potassium chloride administration. She admitted high dose furosemide self-medication for edema. Glomerular filtration rate, tubular sodium reabsorption, potassium secretion, the renin-aldosterone system, total body water distribution and capillary permeability, were studied sequentially until 90 days after her admission. There was hyperactivity of the renin-aldosterone axis, reduction in extracellular and intracellular volumes, normal capillary permeability and high sodium tubular reabsorption, probably explained by a "rebound" salt retention associated with her decreased extracellular volume.

Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats.

BACKGROUND: A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values. METHODS: High (HPD, 1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for 15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2) NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD for 15 days, rats were divided into two groups in which one group was maintained on a HPD and the other group was changed to very low PD (VLPD, <0.05%) for an additional 15 days. In each dietary group, one-half the rats were given bosentan i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)-1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell proliferation was measured by proliferating cell nuclear antigen (PCNA) staining and ET-1 expression by immunohistochemical techniques. RESULTS: In the study of developing hyperparathyroidism, bosentan reduced ET-1 expression in the parathyroid glands of rats on the NPD and HPD (P<0.05). But only in rats on the NPD did bosentan result in a reduced increase in parathyroid gland weight (P<0.05). In the study of established hyperparathyroidism, in which 5/6 NPX rats were given a HPD for 15 days, bosentan started on day 15 reduced (P<0.05) ET-1 expression in rats maintained for 15 additional days on the HPD or the VLPD. On the VLPD, parathyroid gland weight was less (P<0.05) than that in rats on the HPD sacrificed at 15 or 30 days. Bosentan did not reduce parathyroid cell proliferation or parathyroid gland weight in rats maintained on the HPD or further reduce these parameters beyond that obtained with dietary phosphorus restriction. PTH values were lowest in the VLPD group, intermediate in the NPD group, and highest in the HPD group, but in none of the three groups did bosentan decrease PTH values. CONCLUSIONS: In azotemic rats with developing hyperparathyroidism, bosentan resulted in a reduced increase in parathyroid gland weight when dietary phosphorus content was normal. Despite a reduction in ET-1 expression in rats on a HPD with developing or established hyperparathyroidism, bosentan did not reduce the increase in parathyroid cell proliferation, parathyroid gland growth or PTH values. Thus, ET-1 blockade with bosentan did not prevent parathyroid gland growth in the azotemic rat.

[Brain death, bioethics and organ transplantation]. / Muerte encefálica, bioética y trasplante de órganos.

The concept of death has evolved medically, legally and culturally since the introduction of life support technologies in the middle of the 20th century. The traditional cardiopulmonary and the new neurologically based brain death criterions of death are examined. We conclude that brain death, defined as total and irreversible loss of function of the whole brain, fulfills better "the permanent cessation of functioning of the organism as a whole" definition of death. Brain death diagnosis, based on standard neurologic clinical examination performed accurately, is unequivocal. Transplantation medicine, mostly based on organ donation of brain dead people, has become a routine and universally accepted therapeutic intervention nowadays, which benefits many people. Ethics foundations of organ transplantation are reviewed. Even though brain death and organ donation are widely accepted in medical, legal, religious and public opinion today, the whole society and medical community need to be further educated about these matters, so that unavoidable changes of traditional concepts might be better understood. Permanent education should be the best way to dissipate social fears and distrust towards organ donation and brain death.

Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. I. Renal function and biochemical changes.

BACKGROUND: Both dietary phosphorus restriction and the ingestion of ammonium chloride (NH(4)Cl) given to rats on a high-phosphorus diet have been shown to preserve renal function in the azotaemic rat. Parathyroidectomy also has been reported to preserve renal function and, in addition, to prevent kidney hypertrophy in the remnant kidney model. Our goals were (i) to evaluate in azotaemic rats the effect of dietary phosphorus on renal function in a shorter time frame than previously studied and (ii) to determine whether NH(4)Cl administration (a) enhances the renoprotective effect of dietary phosphorus restriction and (b) improves renal function in the absence of parathyroid hormone (PTH). METHODS: High (H; 1.2%), normal (N; 0.6%) and low (L; <0.05%) phosphorus diets (PD) were given for 30 days to 5/6 nephrectomized rats. In each dietary group, one-half of the rats were given NH(4)Cl in the drinking water. The six groups were HPD + NH(4)Cl, HPD, NPD + NH(4)Cl, NPD, LPD + NH(4)Cl and LPD. The effect of NH(4)Cl administration was also evaluated in 5/6 nephrectomized, parathyroidectomized (PTX) rats on NPD. RESULTS: In each of the three dietary phosphorus groups, creatinine and urea clearances were greater (P<0.01) in rats receiving NH(4)Cl. Neither creatinine nor urea clearance was reduced by high dietary phosphorus. Urine calcium excretion was greatest in the LPD group and was increased (P < or = 0.001) in all three groups by NH(4)Cl ingestion. An inverse correlation was present between plasma calcium and phosphorus in the parathyroid intact (r = -0.79, P<0.001) and PTX groups (r = -0.46, P = 0.02). In PTX rats, NH(4)Cl ingestion increased (P < or = 0.01) creatinine and urea clearances and both an increasing plasma calcium concentration (r = 0.67, P<0.001) and urine calcium excretion (r = 0.73, P<0.001) increased urine phosphorus excretion. CONCLUSIONS: At 30 days of renal failure (i) NH(4)Cl ingestion increased creatinine and urea clearances, irrespective of dietary phosphorus; (ii) high urine calcium excretion, induced by dietary phosphorus restriction and NH(4)Cl ingestion, did not adversely affect renal function; (iii) high dietary phosphorus did not decrease renal function; (iv) the absence of PTH did not preserve renal function or prevent NH(4)Cl from improving renal function; and (v) both an increasing plasma calcium concentration and urine calcium excretion resulted in an increase in urine phosphorus excretion in PTX rats.

Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. Part II--Kidney hypertrophy and calcium deposition.

BACKGROUND: Kidney hypertrophy is stimulated by both partial nephrectomy and NH(4)Cl administration. Also, parathyroidectomy (PTX) has been reported to prevent kidney hypertrophy induced by a high protein diet. Our goal was to determine in the azotaemic rat: (i) the combined effects of NH(4)Cl administration and dietary phosphorus on the development of kidney hypertrophy and calcium deposition in the kidney and (ii) whether the absence of parathyroid hormone (PTH) affected the development of kidney hypertrophy and calcium deposition. METHODS: High (HPD, 1.2%), normal (NPD, 0.6%) or low (LPD, <0.05%) phosphorus diets were given to 5/6 nephrectomized rats for 30 days. In each dietary group, one-half of the rats were given NH(4)Cl in the drinking water. The six groups of rats were: (i) HPD + NH(4)Cl; (ii) HPD; (iii) NPD + NH(4)Cl; (iv) NPD; (v) LPD + NH(4)Cl and (vi) LPD. In a separate study, PTX was performed to determine whether PTH affected renal hypertrophy in 5/6 nephrectomized rats given NH(4)Cl. RESULTS: Both with and without NH(4)Cl (+/-NH(4)Cl), kidney weight was greatest (P<0.05) in the HPD groups. In each dietary phosphorus group, kidney weight was greater (P<0.05) in the NH(4)Cl group. In both the +/-NH(4)Cl groups, kidney calcium content was greatest (P<0.05) in the HPD group, but was less (P<0.05) in the NPD and HPD groups given NH(4)Cl. An inverse correlation was present between creatinine clearance and kidney calcium content (r = -0.51, P<0.001). When factored for kidney weight, creatinine clearance was less (P<0.05) in the HPD group in both the +/-NH(4)Cl groups, but was greater in the HPD + NH(4)Cl than in the HPD group. In PTX rats, kidney weight was greater (P<0.05) and kidney calcium deposition was less (P<0.05) in rats given NH(4)Cl. CONCLUSIONS: In azotaemic rats studied for 30 days, NH(4)Cl administration induced kidney hypertrophy. A HPD also induced kidney hypertrophy. The effects on kidney calcium deposition were divergent for which NH(4)Cl administration decreased and a HPD increased calcium deposition. The inverse correlation between kidney calcium content and creatinine clearance suggests that kidney calcium deposition is harmful to renal function. When factored for kidney weight, the lower creatinine clearance in the high phosphorus group suggests that kidney hypertrophy does not completely compensate for the harmful effects of a HPD. This result also suggests that a longer study would probably result in more rapid deterioration in the high phosphorus group. In PTX rats, the absence of PTH did not prevent NH(4)Cl from inducing kidney hypertrophy and reducing kidney calcium deposition. In conclusion, NH(4)Cl and dietary phosphorus each independently affect kidney growth and calcium deposition in the growing rat with renal failure.

Outcome of chilean patients with lupus nephritis and response to intravenous cyclophosphamide.

Several recent open studies suggest that the response rates of lupus nephritis to intravenous (IV) cyclophosphamide are lower than those observed in clinical trials. One explanation could be ethnic differences; for example, black patients more frequently have treatment-resistant lupus nephritis. Another could be the inclusion of patients who are noncompliant with therapy. From our register of 268 systemic lupus erythematosus (SLE) patients examined between 1973 and 1996, 61 patients were treated for proliferative lupus nephritis (17 had World Health Organization [WHO] type III and 43 had WHO type IV) and were followed through to 2001. Exclusion criteria included a serum creatinine level >3 mg/dL. In this retrospective study, we assessed renal outcome and survival with an endpoint of end-stage renal disease (ESRD) or death (Kaplan-Meier). In the univariate analysis, worse prognostic factors for survival were serum creatinine >1.3 mg/dL (p < 0.001), age <30 years (p < 0.001), class 2 renal function stage (p < 0.03), and renal biopsy activity index >7 (p < 0.02). In the subgroup of 26 patients treated with IV cyclophosphamide, survival at 5 and 10 years was 82% and 73%, respectively. The dosage of IV cyclophosphamide was slightly lower than usual and used for a shorter period (median = 23 months) than what is usually recommended because of the high frequency of complications. Renal outcome of the IV cyclophosphamide-treated patients was poorer than that reported in the National Institutes of Health series (ESRD: 15% versus 3%). This low survival rate could reflect the short course and lower doses of IV cyclophosphamide used or ethnic differences. These data emphasize the need for continuous research for better-tolerated drug schemes for treatment of our lupus nephritis patients.