How effective is rescue therapeutic plasma exchange in treatment of SARS-Coronavirus-2?

INTRODUCTION: After the FDA gave emergency approval for the use of therapeutic plasma exchange in treatment for SARS-Coronoavirus-2, we analyzed its efficacy in patients who had failed all other known therapies. METHODS: This was a prospective observational study of 42 patients with SARS-Coronoavirus-2 who had failed conventional therapy and were treated with therapeutic plasma exchange. Pre- and postexchange clinical and laboratory parameters were monitored. The patients were then also compared with a group of 147 patients with SARS-Coronoavirus-2 who were referred for stage 3 acute renal failure and dialysis from SARS-Coronoavirus-2. RESULTS: After therapeutic plasma exchange, there were significant improvements in some clinical parameters but mortality remained high; although better than the renal failure group (43.9% vs. 50.7%, p = 0.004). CONCLUSION: SARS-CoV-2 patients who failed all other therapies had significant mortality with therapeutic plasma exchange; however, their survival was better than SARS-CoV-2 patients with stage 3 acute renal failure.

The first fistula: influence of location on catheter use and the influence of catheter use on maturation.

BACKGROUND: The forearm location for the initial vascular access has traditionally been considered the most desirable; however, recent advances in our understanding the physiology of fistula development suggest that the larger proximal vessels with higher blood flows may be associated with increased wall stress and faster fistula development. We examined whether the location of a first fistula had any relationship to the incidence and duration of catheter use. METHODS: This was an observational study of 808 patients who underwent the creation of an autologous arteriovenous fistula for their first hemodialysis access who were evaluated for the length of use of a temporary catheter. The variables studied for their effect upon catheter use included: location in the forearm or upper arm, age, the presence of diabetes, vascular disease or smoking history. RESULTS: Despite being younger (P < 0.0001), nondiabetics (P < 0.0001), without vascular disease (P < 0.0001), and placed longer before initiation of dialysis (P = 0.03), the patients with forearm fistulas were significantly more likely to need a catheter to start dialysis (P < 0.0001) and the length of use was significantly longer than in upper arm fistulas. Fistulas place prior to initiation of dialysis required shorter maturation time. CONCLUSION: The upper arm as the initial site for fistula creation was associated with a significantly reduced incidence and prevalence of catheter use when the patients began dialysis. Fistulas placed prior to the initiation of dialysis had significantly shorter maturation times than those created after a catheter had been inserted which might be due to delayed maturation caused by the catheter.

The prevalence and meaning of eosinophilia in renal diseases on a nephrology consultation service.

BACKGROUND: In recent years, we have come to understand that the eosinophil is more than the end point in clearance of parasitic infection or a maladaptive response to asthma and allergic reactions. Since eosinophilia has been reported to be common in renal diseases, we thought that an evaluation of the associations of eosinophilia on a renal consultation service would add some value to the understanding of their role in renal disease. METHODS: This was a prospective cross-sectional study of 1339 consecutive patients referred to the nephrology service after hospitalization who were evaluated for the relationship of the amount of serum eosinophils to their diagnosis, gender, age and the presence of autoimmune disease, cancer, infection, liver disease, pleural effusions, allergies and use of prednisone, beta-blockers or beta agonists, in addition to the total white blood count, urine protein, serum concentration creatinine and phosphorus levels and estimated glomerular filtration rate. RESULTS: The presence of vascular disease correlated the most strongly with increased eosinophil count (partial correlation coefficient, r = 0.18, P = 0.006), followed by pleural effusions (r = 0.17, P = 0.001), while total white cell count (r = -0.18, P = 0.008) and administration of beta-blockers (r = -0.13, P = 0.047) demonstrated significant inverse correlations and the presence of autoimmune disease, cancer, allergies, proteinuria and serum phosphorus concentration demonstrated no significant correlation. CONCLUSION: There are multiple associations with increased eosinophil counts in patients seen on a nephrology consultant service; however, their presence appears less often in association with allergies or uremia and more often with vascular disease.

Can the combination of calcium and parathormone levels above K/DOQI guidelines be used as a marker of adynamic bone disease in African Americans?

BACKGROUND: Patients of African American descent are at risk for the development of adynamic bone disease at parathyroid hormone levels 50% above the K/DOQI guidelines. Since a low bone formation rate is associated with hypercalcemia, attempts to reach one K/DOQI guideline may result in serum calcium levels above another K/DOQI guideline. Calcium levels above K/DOQI guidelines therefore may signal a need to stop parathyroid suppression. SETTING AND PARTICIPANTS: Bone biopsies were performed at the East Alabama Medical Center, in Opelika AL, USA on eight patients (four Caucasians, four African Americans) whose parathormone levels and serum calcium levels both exceeded K/DOQI guideline recommendations. RESULTS: All patients had mild to severe hyperparathyroid bone disease. No variable studied was predictive of the finding. LIMITATIONS: Small sample size and the unavailability of the original Nichols Diagnostic Institute radioimmunoassay for parathormone. CONCLUSION: We did not find hypercalcemia predictive of adynamic bone in patients of African American descent at levels of parathormone where low bone formation rates have been documented to occur. Since no parameter predicted bone histology, perhaps bone biopsies will be necessary to distinguish hyperparathyroidism from adynamic bone disease in African Americans with ESRD, hypercalcemia, and moderately elevated levels of PTH. Further studies are needed to determine appropriate therapy.

Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia.

While the fractional excretion of solutes have long been considered excellent research tools to investigate tubular physiology, their clinical use has become common over the last 40 years in the diagnoses of many disorders; however, none have reached the clinical utility of the fractional excretion of sodium in the ability to distinguish pre-renal azotemia from acute tubular necrosis. Nevertheless, there are many drugs and medical conditions that interfere with that utility and recently other solutes, including urea, uric acid and lithium, have been recently investigated to improve the diagnostic ability in clinical situations where the fractional excretion of sodium is known to be unreliable. We review the tubular physiology of these solutes and show how the differences in tubular physiology might be exploited to develop a strategy for their optimal clinical use.

Can omeprazole reduce the incidence of hypercalcemia in dialysis patients using calcium containing phosphate binders?

INTRODUCTION: Calcium absorption from the bowel is known to depend upon gastric acidity. We chose to investigate whether the use of omeprazole could reduce the incidence of hypercalcemia in dialysis patients who could not afford expensive non-calciumbased phosphate binders. METHODS: 26 hemodialysis patients at the Hypertension, Nephrology, Dialysis, and Transplantation Clinic in Opelika, Alabama (USA) with refractory hypercalcemia for at least 3 months prior to the study who were unable to afford non-calcium-based binders were treated with 20 mg of omeprazole a day for three months and then compared to 27 similar patients who were taking non-calcium-based binders. RESULTS: While there was a trend towards lower serum calcium levels and phosphate binder dosages in the omeprazole group (particularly with the calcium carbonate binders as opposed to the calcium acetate binders), there was no statistical difference in any variable in either controls or the omeprazole group from pre-study period. CONCLUSIONS: While theoretically advantageous, we found that omeprazole had little clinical benefit in reducing hypercalcemia in a population who are unable to afford non-calcium-based binders; however, further studies may be warranted.

The comparative benefits of the fractional excretion of urea and sodium in various azotemic oliguric states.

BACKGROUND: The fractional excretion of urea (FeUrea) may result in more reliable in the determination of renal function than sodium in the presence of oliguric azotemia; however, its usefulness remains controversial, perhaps due to an evolving understanding of urea transport within the kidney. METHODS: This was a prospective observational study of 100 consecutive patients referred to the nephrology service for azotemic oliguria. Multiple clinical variables were analyzed to determine variables responsible for the differences between the FeUrea and fractional excretion of sodium (FeNa) in the ability to distinguish pre-renal azotemia from intrinsic renal disease. RESULTS: Overall, the FeUrea was more accurate (95 vs. 54%, p < 0.0001), yet both tests accurately detected the presence of intrinsic renal disease (FeNa 75%, FeUrea 85%, p = NS). The FeUrea performed significantly better (98 to 49%, p < 0.0001) in detecting pre-renal azotemia, and that advantage came exclusively in patients taking diuretics (p < 0.0001); however, 4/5 cases incorrectly detected by the FeUrea were correctly detected by the FeNa. All 4 cases had infection. CONCLUSION: The FeUrea appears more accurate in patients receiving diuretics; however, the FeNa may have an advantage in patients with infection.

Understanding the pathophysiology of hemodialysis access problems as a prelude to developing innovative therapies.

Maintenance of a functioning vascular access for hemodialysis is a major challenge for nephrologists, vascular surgeons and--most importantly--the patients themselves. Greater insight into the pathophysiology of access thrombosis, stenosis, aneurysm formation, fistula maturation failure and catheter infection will aid the development of innovative ways to prevent and treat these complications. According to the results of observational studies, agents that decrease the release of inflammatory mediators, improve endothelial function, and inhibit the migration and proliferation of vascular smooth-muscle cells might improve the maturation and survival of native hemodialysis fistulas and synthetic hemodialysis grafts by reducing the risks of thrombosis and stenosis. Currently available drugs that interfere with metalloproteinases could prevent the formation of aneurysms, and bacterial quorum sensing offers a promising target for the prevention of biofilm infection in hemodialysis catheters.

Beyond anemia: the clinical impact of the physiologic effects of erythropoietin.

Although we have known that oxygen tension affects erythrocyte production since the 19th century, we have only recently begun to understand many subtleties of erythropoietin (EPO) physiology. EPO administration has allowed hundreds of thousands of patients to avoid transfusions. With the beneficial effects so apparent a detailed understanding of the full clinical physiology of this plasma factor seemed less important. However, the unanticipated increase in mortality found in recent randomized studies is prompting a reassessment of this view. We will review what is known about the physiology of this plasma factor that, it is now clear, is more than just an erythrocyte production factor.

Gustatory sweating recurring on peritoneal dialysis but resolving during periods of hemodialysis.

Gustatory sweating is a rare disorder characterized by profuse sweating on the forehead, face, scalp, and neck occurring soon after ingesting food, which has been reported in diabetic patients. The mechanism is thought to be triggered by taste buds and not gastric stimulation. We report a case where gustatory sweating repeatedly developed on peritoneal dialysis that resolved on periods of hemodialysis. A 32-year-old woman with diabetic end-stage renal disease developed gustatory sweating shortly after beginning continuous ambulatory peritoneal dialysis despite excellent clearances. After 5 months, she changed to hemodialysis for 2 months and noticed complete resolution of her gustatory sweating; however, after her return to peritoneal dialysis 2 months later, her gustatory sweating recurred. While on peritoneal dialysis, she was treated with clonidine, which resulted in improvement but not resolution of her symptoms as had occurred on hemodialysis. Another period on hemodialysis resulted in the resolution of her symptoms that returned again after restarting peritoneal dialysis. Clonidine provided incomplete relief while topical glycopyrrolate was effective and without complications. We report recurrent gustatory sweating on peritoneal dialysis that resolved with hemodialysis. We have no data to suggest that intra-abdominal stimulation played a role, but rather that despite excellent clearances neuropathy may have played a role. Treatment with topical glycopyrrolate may be safe and effective given every third day if clonidine is ineffective.

A hypothesis: can erythropoietin administration affect the severity of retinopathy in diabetic patients with renal failure?

BACKGROUND: Before the clinical availability of erythropoietin, diabetic retinopathy was known to stabilize on dialysis. Recently erythropoietin has been shown to be a potent angiogenic factor. Therefore, we chose to examine whether severity and progression of diabetic retinopathy has been accelerated by the administration of recombinant erythropoietin to patients with chronic renal failure. METHODS: Records of the patients followed by the Hypertension Nephrology, Dialysis, and Transplantation Clinic, the regional nephrology referral center for Eastern Alabama, from 1982 through 2005 were reviewed. Funduscopic examination at the time of ESRD was ranked according to the proposed international scale for severity of clinical diabetic retinopathy. Forty-five patients from the era before the availability of erythropoietin were matched to 45 patients from 2002 to 2004 who had been given erythropoietin but had similar prevalence of proliferative retinopathy, neuropathy, and years of diabetes before the onset of end-stage renal disease. Progression of retinopathy was compared according to multivariate analysis with 2-tailed Pearson correlation coefficient. RESULTS: There was significantly greater deterioration of retinopathy at 1 year in the patients who had received erythropoietin (P = 0.004). Although the presence of retinopathy at ESRD correlated with known traditional risk factors such as years of diabetes, age, and serum cholesterol, the deterioration of retinopathy after the initiation of hemodialysis correlated only with hematocrit (P = 0.042) and most significantly total dose of erythropoietin (P = 0.001). CONCLUSIONS: The prevalence and severity of proliferative retinopathy appear to have increased and are most closely associated with the erythropoietin dosing.

Is systemic heparin a risk factor for catheter-related sepsis in dialysis patients? An evaluation of various biofilm and traditional risk factors.

BACKGROUND: Biofilms are dense aggregates of surface adherent microorganisms embedded in a polysaccharide matrix. Intravenous iron and heparin are thought to promote the formation of biofilm. Both are commonly employed during hemodialysis treatments which might affect the incidence of catheter-related sepsis. METHODS: 559 patients who underwent hemodialysis treatment with a catheter were reviewed. Episodes of sepsis were analyzed for the use of systemic heparin and intravenous iron as well as all other risk factors for sepsis. RESULTS: Sepsis developed in 141 of the 796 catheters. Analysis of variance revealed that the number of days that the catheter remained in place was the most significant variable (p < 0.0001) associated with catheter-related sepsis along with multiple other variables, but a Cox proportional hazards analysis revealed that only the two biofilm risk factors (intravenous iron [p < 0.001], and mid-treatment bolus of heparin [p = 0.046]) along with previously reported factor of a depressed serum albumin (p = 0.001) are of significance. CONCLUSION: In addition to duration of catheter use, we found three significant risk factors for sepsis and two of those three have been associated with the development of biofilm.

Will the addition of pentoxifylline reduce proteinuria in patients with diabetic glomerulosclerosis refractory to maximal doses of both an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker?

BACKGROUND: While interruption of angiotensin synthesis and angiotensin blockade are well know to reduce proteinuria and preserve renal function in patients with diabetic glomerulosclerosis, many patients still have significant proteinuria after having reached maximal doses of those medications. We chose to examine the effect of the addition of pentoxifylline to the therapeutic regimen of patients with significant proteinuria and chronic renal insufficiency who had reached maximal does of an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB), on the reduction of proteinuria and the preservation of renal function. METHODS: Seven male patients with diabetic glomerulosclerosis with proteinuria of at least 1.5 g/24 hours and a creatinine clearance of at least 15 ml/min despite maximal doses of an ACEI and an ARB for over 12 months were treated with pentoxifylline adjusted for creatinine clearance. They were then compared with 7 similar patients matched for age, duration of medications, proteinuria, creatinine clearance and mean arterial pressure. The groups were compared for any significant differences on at baseline and at 12 months. RESULTS: Although proteinuria decreased in the pentoxifylline group (5.657 +/- 3.5227 to 3.799 +/- 3.647 g/24 hours) there was no significant difference from the control group (4.743 +/- 2.320 to 4.986 +/- 2.941 g/24 hours). Similarly both groups lost creatinine clearance (41.0 +/- 27.44 to 29.33 +/- 22.21 ml/min with pentoxifylline and 45.57 +/- 21.854 to 27.33 +/- 27.105 ml/min in controls), but there was no significant difference in either clearance or mean arterial pressure. CONCLUSION: Although there was a trend toward the reduction of proteinuria, we found no statistical benefit in proteinuria reduction or preservation of renal function by the addition of pentoxifylline to maximal doses of ACEIs and ARBs.

Malignancy-related hypercalcemia developing on a bisphosphonate but responding to calcitonin.

Bisphosphonates are considered a cornerstone for the treatment of hypercalcemia of malignancy, whereas calcitonin has not been found to be as potent. We report a case of severe hypercalcemia of malignancy that developed while the patient was taking alendronate that responded to the use of calcitonin. A 73-year-old woman developed hypercalcemia of malignancy while taking weekly alendronate. The patients' serum calcium remained above 15 mg/dL despite hydration and loop diuretics for 48 hours in addition to the bisphosphonates, and resistance was suspected. Intravenous calcitonin produced a dramatic decrease within 12 hours and normal serum calcium within 24 hours of treatment. Calcitonin might be useful for hypercalcemia of malignancy resistant to bisphosphonates.

Effect of phosphate binders upon TSH and L-thyroxine dose in patients on thyroid replacement.

BACKGROUND: While calcium carbonate is known to interfere with the gastrointestinal absorption of levothyroxine, we hypothesized that other phosphate binders would also bind to levothyroxine and decrease bioavailability of levothyroxine in dialysis patients. METHODS: The records of 1,566 patients on hemodialysis who were being treated by the Hypertension, Nephrology, Dialysis, and Transplantation Center (the regional renal referral center for Eastern Alabama, USA) were evaluated. The type of phosphate binder and amount were then correlated (two-tailed Pearson Correlation) to TSH levels, serum phosphorus and the amount of levothyroxine taken. Friedman Test and Wilcoxon Signed Ranks Test were performed to analyze the significance of difference in thyroxine dosing and TSH levels between the different phosphate binders. RESULTS: Sixty-seven patients were identified who were taking levothyroxine while taking three different kinds of phosphate binders; namely, calcium carbonate, calcium acetate, and sevelamer HCl. We found that the TSH levels of patients on calcium carbonate (P = 0.002) and sevelamer HCl (P = 0.033) were significantly higher than patients on calcium acetate with the difference increasing with time on each binder. Sevelamer was also found to be associated with significantly higher dosing requirement of thyroid replacement than those on either calcium carbonate or calcium acetate (Z = -3.17, P = 0.001). CONCLUSION: Sevelamer (but not calcium acetate) in addition to calcium carbonate appears to interfere with the bioavailability of levothyroxine.