Referral patterns of primary care physicians for chronic kidney disease in general population and geriatric patients.

BACKGROUND: Late referral of patients with chronic kidney disease (CKD) by primary care physicians (PCPs) is associated with poor outcomes. We sought to assess factors influencing PCPs referral patterns in the general population and in geriatric patients, and compared their perceptions to the referral patterns. METHODS: We retrospectively reviewed 268 patients with Stage 3 CKD (early referral) and 280 with Stage 4 CKD (appropriate referral) seen in renal clinic and compared them to 268 randomly selected non-referred Stage 4 CKD patients from primary care physicians office records. We also surveyed 400 regional PCPs on factors influencing their referral for CKD. RESULTS: Non-referred patients were significantly (p < 0.05) more likely to be over 65 years (OR: 3.5; 95% CI: 2.3 - 5.2), females (OR: 1.4; 95% CI: 1.0 - 2.0) and of non-white race (OR: 2.6; 95% CI: 1.5 - 4.5) after adjusting for relevant confounding variables. Charlson comorbidity index greater than 4 was associated with non-referral when the non-referral group was compared to the early referral group. Among geriatric patients, women and a higher comorbidity index were associated with non-referral. 25% of PCPs completed the survey and 62% PCPs were unfamiliar with K/DOQI referral guidelines. Age > 75 years, limited life expectancy, patient noncompliance or refusal to consider dialysis influenced PCPs decision to refer. CONCLUSIONS: Our study shows that elderly women, minorities and patients with multiple comorbidities are at risk for non-referral for CKD care. Educating PCPs on the appropriate referral of CKD patients, especially those at risk for late or non-referral to a nephrologist is warranted, as are trials assessing different educational strategies.

Contemporary approach to diagnosis and evaluation of renovascular hypertension.

Recommendations regarding the clinical protocols for radionuclides of choice and diagnostic criteria for renovascular hypertension have been established by the consensus report on captopril renography. A review of the existing data indicates that postcaptopril renography alone is a safe and effective means of noninvasively screening hypertensive patients. A normal radionuclide study after captopril suggests with a reasonable degree of certainty that potentially reversible renovascular hypertension is unlikely. A positive study in an appropriately screened hypertensive patient with preserved renal function suggests renovascular disease is likely with a sensitivity and specificity in excess of 90%. In the comparative studies of Elliott and Miralles and colleagues, captopril renography was a more sensitive and specific screening test than the captopril plasma renin activity test. Although there may be confounding variables, such as renal dysfunction, medications, and types of stenosis, a positive captopril renogram may suggest a cure or improvement in blood pressure control with successful intervention such as PTRA or revascularization. Whether captopril renography can predict stabilization of individual kidney function is speculative and deserving of further study.

Tunneled right atrial catheter infection presenting as renal failure.

We report two cases of progressive renal failure secondary to membranoproliferative glomerulonephritis associated with subclinical septicemia from a tunneled right atrial catheter used for home parenteral nutrition administration. Although the occurrence of line infection and septicemia is a common complication of central venous catheters, a review of the literature reveals only one case report of renal failure secondary to an infected implanted central venous device. Both patients presented with azotemia and had biopsy-proven membranoproliferative glomerulonephritis, accompanied by leukocytoclastic vasculitis. In both cases, removal of the right atrial catheter and prolonged antibiotic therapy was effective in resolving the ongoing infection and resulted in marked improvement in renal function. A high index of suspicion for catheter sepsis should be maintained in patients with tunneled right atrial catheters presenting with subacute renal failure.

Lovastatin preserves renal function in experimental diabetes.

Although hyperlipidemia has been associated with the progression of glomerulosclerosis, little attention has been directed toward the use of lipid-lowering agents in altering diabetic nephropathy. We tested the hypothesis that lovastatin and the combination of lovastatin and enalapril would preserve renal function in streptozotocin-induced diabetic Wistar rats. Five groups of animals were studied: group 1, nondiabetic (n = 10); group 2, diabetic, insulin only (n = 12); group 3, lovastatin, (15 mg/kg/day, n = 13); group 4, enalapril, (50 mg/L drinking water, n = 10) and group 5, lovastatin plus enalapril, (n = 14). After 8 weeks of treatment, glomerular filtration rate (GFR, insulin clearance) was measured in anesthetized animals. The diabetic group was characterized by a GFR of 0.18 +/- 0.03 ml/min/g of kidney weight (gKW), a blood glucose level of 441 +/- 36 mg/dL, plasma cholesterol and triglyceride levels of 64 +/- 6.0 and 103 +/- 26.0 mg/dL. Lovastatin preserved GFR, 0.52 +/- 0.06 ml/min/gKW compared with the diabetic control subjects (P < 0.05). Enalapril also maintained GFR (0.42 +/- 0.06 ml/min/gKW, P < 0.05). In the lovastatin plus enalapril group, GFR (0.62 +/- 0.05 ml/min/gKW) was greater than in the enalapril group (P < 0.05), but was not different from the lovastatin group. Plasma lipid levels were not altered in any of the groups. Assessment of the kidneys by histology after treatment showed that the mesangial matrix injury score was better in the lovastatin, enalapril, and lovastatin plus enalapril groups compared with the diabetic group (P < 0.05). Lovastatin, enalapril, and lovastatin plus enalapril abrogated the decline in GFR and glomerular injury in diabetic rats. Lovastatin's direct renal protective effect seems to be independent of its lipid-lowering properties.

Cardiac disease in chronic uremia: investigation.

Cardiovascular disease continues to be the leading cause of death in the end-stage renal disease (ESRD) population, accounting for nearly half of the deaths among the dialysis population. The purpose of this article is to review the clinical screening tools available to the attending nephrologist and consulting cardiologist to detect both symptomatic and asymptomatic cardiovascular disease in ESRD patients. The author presents a detailed overview of (1) assessment of left ventricular (LV) function in the hemodialysis population and (2) noninvasive cardiovascular screening in patients before anticipated renal transplantation. Specific guidelines are offered for the pretransplantation evaluation of cardiac disease based on the patient's cardiovascular risk factors, symptomatology, and stress testing with either thallium or dobutamine echocardiography. Recent studies of cardiovascular screening in selected hemodialysis populations may not be extrapolated to the general ESRD population pending further investigation. Crucial questions relating to the utility of cardiovascular screening and intervention in the general ESRD population remain and deserve further study.

Dietary protein does not alter intrinsic reactivity of renal microcirculation to angiotensin II in rodents.

The effect of dietary protein on renal function and on renal microvascular reactivity to angiotensin II was determined in rats fed a high-protein diet (40% protein), a low-protein diet (6% protein), or a normal diet (23% protein). Inulin clearance was higher in high-protein-fed rats (n = 7) than in rats fed a low-protein diet (n = 7), 0.88 +/- 0.14 (means +/- SE) vs. 0.54 +/- 0.07 ml.min-1.g kidney wt-1 (P < 0.05). We also used videomicroscopy to assess the effect of angiotensin II on the renal microcirculation in a hydronephrotic kidney preparation. The afferent and efferent arterioles constricted to angiotensin II and norepinephrine in both high- and low-protein-fed rats; this constriction was diminished to angiotensin II but not to norepinephrine, in rats fed a high-protein diet (-24.3 +/- 4.5, -20.2 +/- 4.2%) compared with rats fed a low-protein diet (-39 +/- 5.1, -39.1 +/- 5.7%). The vasoconstrictor responses to angiotensin II in rats fed a high-protein diet and a normal diet were significantly greater following inhibition of angiotensin II formation with captopril but not in low-protein-fed rats. The apparent high-endogenous level of angiotensin II among rats fed a high-protein diet may account for the diminished reactivity to exogenous angiotensin II. Thus alterations in intrinsic vascular reactivity to angiotensin II are not responsible for the altered hemodynamics associated with dietary protein.

Clinical applications of renal scintigraphy.

Nuclear medicine techniques for evaluating the kidney and urinary tract have evolved from pioneering studies with primitive radiopharmaceuticals and hand-held probe detectors to a sophisticated technology capable of providing important physiologic and anatomic information. Advances in nuclear medicine and computer technology over the past decade have resulted in improved, clinically useful scintigraphic studies to assist clinicians in examining patients who have diseases of the genitourinary tract. However, renal scintigraphy is a complex subject. Five different radiopharmaceuticals are available for scanning the kidneys, multiple quantitative indexes can be generated, and protocols may vary depending on the clinical setting. The focus of this review is practical: to summarize the clinical advantages and disadvantages of the different radiopharmaceuticals; to review quantitative indexes that help interpret images; and to review the role of radionuclide scintigraphy in patients with suspected obstruction, pyelonephritis, and renovascular hypertension.

Changing demographics in renal transplant recipients: the 30 year Cleveland Clinic experience.

While it does appear that the most recent era of transplantation has not resulted in significant improvement in long-term allograft function, this appears to be due, at least in part, to the transplantation of increasing numbers of high-risk patients. It is noted that the improved results accomplished over prior eras of transplantation have been maintained despite the inclusion of these high-risk patients. Patients currently undergoing transplantation are more likely to be older, diabetic, obese or African American. All of these subgroups have poorer patient survival in the most recent transplant era and thus, death with a functioning graft has become a significant contributor to graft loss. Recipients were more likely to receive kidneys from cadaveric donors in the most recent era and within the live-donor groups, sibling donation has decreased. Hopefully, the recent trend of increased live-donor transplants (especially living, unrelated transplants) will continue. Cadaveric recipients were at higher risk for posttransplant ATN which, for the first time in the current era, had a significant adverse impact on graft survival. Long-term survival appeared to be associated with particular characteristics (optimal age at transplantation, optimal donor age, live donor, etc.), and can be achieved despite known risk factors, such as rejection or delayed graft function.

Advances in noninvasive screening for renovascular disease.

BACKGROUND: Nearly 50 million Americans have hypertension, and renovascular hypertension accounts for perhaps 1% of them. PURPOSE: To review the current recommendations and the available screening tests for renovascular hypertension. SUMMARY: The presence of clinical clues increases the predictive value of screening tests for renovascular hypertension; these include abrupt onset of hypertension before age 30 or after age 55, severe hypertension, accelerated or malignant hypertension, hypertension refractory to a triple-drug regimen, moderate hypertension with diffuse vascular disease, an epigastric bruit, moderate hypertension with unexplained azotemia, and azotemia induced by an angiotensin-converting enzyme inhibitor. Captopril renography and duplex ultrasonography are clinically useful screening tools, but wide variation in accuracy exists among institutions. Magnetic resonance angiography may emerge as an effective clinical test. CONCLUSIONS: A thorough history and physical examination, coupled with judicious use of available screening technology, can help determine if a patient has renovascular hypertension and may benefit from intervention.

Provocative captopril testing in the diagnosis of renovascular hypertension.

Firm recommendations concerning the testing procedures, radionuclides of choice, and diagnostic criteria for RVHT are somewhat difficult, given the lack of rigorous standardization of these complex protocols. Nevertheless, review of the existing data indicates that post-captopril renography alone appears to be a safe and effective means of noninvasively screening hypertensive patients for renovascular disease. A normal study after captopril suggests with a reasonable degree of certainty that potentially reversible RVHT is unlikely. A positive study in an appropriately screened hypertensive patient with preserved renal function suggests that renovascular disease is likely, with sensitivity and specificity in excess of 90%. In the comparative study of Elliott et al, captopril renography was a more sensitive and specific screening test than the captopril PRA test. Although there may be confounding variables such as renal dysfunction, medications, and types of stenosis, a positive captopril renogram might also suggest a cure or improvement in blood pressure control with successful intervention such as PTRA or revascularization. Whether captopril renography might predict stabilization of individual kidney function is speculative and deserves further study.

Studies on the afferent and efferent renal nerves following autotransplantation of the canine kidney.

The presence of both afferent and efferent renal nerves following renal transplantation was investigated in a canine autotransplant model. The efferent postganglionic sympathetic renal nerves were studied using the glyoxylic acid histofluorescence technique to identify renal tissue adrenergic amines (Grade 0-4). The afferent sensory renal nerves were studied by the systemic blood pressure response to renal arterial injection of capsaicin. In 8 control dogs with native innervated kidneys (Group I), intrarenal injection of capsaicin significantly increased the systemic blood pressure from baseline by 32.4 +/- 6.3 mm. Hg (p less than 0.01). This response was equivalent to the blood pressure increase following injection of capsaicin into the mesenteric artery which was 37.3 +/- 9.8 mm. Hg. The renal tissue histofluorescence grade in this group was 4. Six dogs were studied two to three weeks after autotransplantation of a solitary kidney (Group II). Intrarenal injection of capsaicin did not increase the systemic blood pressure in these animals. Three dogs in this group had no evidence of renal tissue adrenergic amines by histofluorescence (Grade 0); the remaining two animals had renal tissue histofluorescence grades of 1 and 2. Eight dogs were studied 12 to 35 months after autotransplantation of a solitary kidney (Group III). Intrarenal injection of capsaicin in these animals significantly increased the systemic blood pressure from baseline by 10 +/- 1.4 mm. Hg (p less than 0.001). The renal tissue histofluorescence grade in this group ranged from 1 to 3. These data support the presence of both afferent and efferent renal nerves in the kidney at greater than or equal to one year post-transplant.

State-of-the-art review: captopril renography--pathophysiological considerations and clinical observations.

Advances in renal angiography and revascularization techniques have renewed interest in developing a better noninvasive screening test for identifying patients with potentially correctable renovascular hypertension. Captopril renography is a promising diagnostic tool in the evaluation of the hypertensive patient. This review highlights the important pathophysiological changes in renal hemodynamics and humoral response attributable to significant renal artery stenosis, and underscores the dramatic effects of angiotensin-converting enzyme inhibition on the renovascular bed. The review also summarizes the available clinical information in captopril renography, and presents consensus recommendations on appropriate patient selection, radionuclide(s) of choice, and suggested diagnostic criteria.

Transplant renal artery stenosis in a canine model: evaluation of hemodynamic changes, renal function, and captopril renography.

The utility of captopril renography in the diagnosis of renal artery stenosis was examined in a canine model of renal autotransplantation with and without renal artery clipping. Autotransplantation of the left kidney to the right iliac fossa with contralateral nephrectomy was done in female mongrel dogs. One group served as controls (n = 6). A second group underwent constriction of the external diameter of the renal artery at the time of the operation to produce renal artery stenosis (n = 7). At two weeks postoperatively, glomerular filtration rate was significantly lower in the renal artery stenosis group (26.2 +/- 3.4 ml./min. vs. 38.2 +/- 3.2 ml./min., p less than 0.05), and deteriorated further after captopril administration (17.9 +/- 2.7 ml./min. vs. 26.2 +/- 3.4 ml./min., p less than 0.05). Despite the presence of hemodynamically significant renal artery stenosis, mean arterial pressure was not different between the two groups (134 +/- 4 mm. Hg vs. 132 +/- 6 mm. Hg, control vs. renal artery stenosis, p = NS). Captopril renography did not enable detection of renal artery stenosis in this autotransplant model.

Pseudo-gamma heavy chain (IgG4 lambda) deposition disease.

Two patients with Ig deposition disease presented with acute renal failure, moderate proteinuria, and hematuria. A plasmacytoid lymphocytic infiltrate was identified in bone marrow that produced IgG4 lambda and free lambda light chains. One patient developed an anaplastic plasmacytoma (secreting only lambda light chains) 1 yr after renal biopsy. Renal biopsy in both patients demonstrated a nodular intercapillary glomerulopathy and electron dense granular deposits, associated with a linear pattern of IgG4 heavy chain deposition in vascular, tubular, and glomerular basement membranes (VBM, TBM, and GBM). In one patient this entrapped IgG4 was unassociated with detectable kappa or lambda light chains. In the second patient, lambda light chains (1+) were detected only in the GBM, but IgG4 (4+) was identified in GBM/TBM. Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process.

Hypoechoic renal pyramids: sonographic visualization in older children and young adults.

The frequency and degree of visualization of medullary pyramids in a normal population, aged 10-29 years, was analyzed. Hypoechoic pyramids were visualized in 42% of right kidneys in subjects aged 10-18 years and in 27% of subjects aged 19-29 years. Prominently hypoechoic pyramids, mimicking the appearance of neonatal kidneys, were seen in an additional 34% of subjects aged 10-18 years and in 16% aged 19-29 years. Prominent pyramids were present in 50% of subjects with renal cortical echogenicity (RCE) equal to liver, but also in 21% of subjects with RCE less than liver. Our study expands the age at which prominently hypoechoic medullary pyramids can be considered a normal finding. This may relate to recent improvements in ultrasound technology.

Renal physiology of renal artery stenosis. Implications for captopril-stimulated renography.

Captopril-stimulated renography is emerging as a useful diagnostic tool for the evaluation of the hypertensive patient suspected of having renovascular hypertension (RVHT). This overview focuses upon the alterations in renal hemodynamics and function induced by renal artery stenosis (RAS) and reviews the effects of angiotensin-converting enzyme (ACE) inhibition upon blood pressure and kidney function in the various experimental models of RVHT. Understanding the effects of ACE inhibition upon the kidney distal to a stenosis and appreciating the potential effect of sodium balance or antihypertensive medications are crucial in anticipating the putative changes in the radionuclide studies of the renovascular bed following ACE inhibition.