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Prednisone (p) treatment of hivassociated glomerulopathies: A therapeutic dilemma
A10
1997 SPRING CLINICAL N E P H R O L O G Y MEETINGS
21
23
IMPROVEMENT IN SERUM CREATININE LEVELS FOLLOWING RENAL ARTERY ANGIOPLASTY IN ELDERLY PATIENTS WITH ISCHEMIC NEPHROPATHY. Ronit H. Lavie. Jaime F. Avecillas, Frank E. Vogel, Daniel J. Javit, Richard Chart, Michael F. Michelis, Nephrology Section, Dept. of Medicine, Lenox Hill Hospital, New York, New York. Intervention for renal artery stenosis, which may cause iscbemic nephropathy and chronic renal failure, is increasingly common. We reviewed our experience in nine patients with angiographically proven renal artery stenosis who underwent pereutaneous transluminal renal artery angioplasty (PTRA) +/- stent placement. The indications included worsening renal function in all subjects, and refractory hypertension in 1/9. Data from these elderly patients included serum creatinine (Cr), Cr upon discharge, and followup Cr obtained 13+4 months following the procedure. Additionally, mean arterial blood pressure (MAP), plasma renin activity (PRA), and serum aldosterone (Aldo) levels were recorded. The mean data + SEM are shown below.
EFFECTS OF ISOFLURANE (ISF) ON RENAL PROXIMAL TUBULAR CELL ENERGETIC& Karen Lochhead Evan Klmmsch and Richard A. Zager. University of Washington Medical Center, Seattle, Wasldngton The post-operative period is a common clinical setting for the onset of acute tubular necrosis (ATN). ISF, a widely used fluorinated anesthetic, could potentially be a risk factor for ATN if it were shown to have direct nephrotoxic effects. ISF is metabolized to release inorganic fluoride, which is known to inhibit Na,K-ATPase and thus cause derangements in cellular energetics. The goal of this study was to examine the effects of ISF on cellular energetics using isolated rat proximal tubular segments (ITS). PTS were incubated with 0-7 mM doses of ISF, (overlapping with low mM ISF blood levels observed in humans undergoing ISF anesthesia). Adenine nucleotide levels were assessed alter a l hour incubation. Similar studies were done with sodium fluoride (NaF, 0.5-10 raM). To investigate whether changes in ATP were due to increased consumption by Na,K-ATPase, adenine nucleotides were measured in PTS incubated with ISF in the presence and absence of ouabain. To determine if the changes in ATP were due to an increase in aerobic metabolic work, oxygen consumption was measured in PTS incubated with ISF and ouabain. ISF induced striking dose dependent declines in cellular ATP (96% loss of ATP at the 7 mM dose) and the decrement in ATP occurred prior to substantial lethal cell injury as measured by LDH release. NaF caused significant reductions in the ATPIADP ratio at all concentrations tested. Onabain exerted no protection over the ISF induced decline in ATP, indicating timt an increase in Na,K-ATPase activity was not the mechanism of ATP loss. Oxygen consumption declined in the presence of ISF with no further decline seen with the addition of ouabain, indicating that ISF inhibited Na,K-ATPase driven respiration. In conclusion: (1) ISF causes a profound derangement in cellular energetics marked by a decline in cellular ATP which is likely a result of decreased ATP production. (2) These decrements in ATP can be reproduced using NaF, indicating that fluoride is the probable mediator of ISF-induced tubular injury. (3) ISF inhibits Na,Ko ATPase, which may contribute to the drug's cytotoxic effects.
age peak Cr discharge Cr followup Cr MAP pre-precedure MAP discharge PRApre-procedure Aldo pre-procedure
70+_4 yrs 4.2+0.8 mg/dl 2.9+0.7 mg/dl (p=0.06) 3.0+1.1 mg/dl 124+8 mmHg 100_+4 mmHg 8.5+2.5 ng/ml/hr 19.8+5.2 ng/dl
Complications included pseudoaneurysm at the femoral puncture site in 3/9 subjects. In summary, intervention improved serum Cr in our patients with ischemie nephropathy. Most benefit was observed when renal function was mildly to moderately decreased.
22
24
EFFECTS OF ERYTHROPOIETIN (EPO) ON PROLACTIN (PRL) LEVELS, HYPOGONADISM (HG) AND BONE DENSITY (BD) IN PATIENTS (PTS) WITH CHRONIC RENAL FAILURE (CRF)
P R E D N I S O N E (P) T R E A T M E N T O F HIVASSOCIATED GLOMERULOPATHIES: A T H E R A P E U T I C D I L E M M A : Suresh Mathew, Michael Choi, Paul J. Scheel, Jr., and W i l l i a m A. Briggs. The Johns Hopkins University School of Medicine, Baltimore, MD. Since the reports by Smith et al (Am. J. Med. 97:145 and 101:41), we have treated selected HIV seropositive patients (pts) with renal failure associated with glomerular diseases, predominantly HIV-associated nephropathy (HIVAN), with P. Current infection, ongoing IV drug abuse, psychiatric disease and non-compliant behavior precluded treatment (B). Ten pts (8 H I V A N , 1 H I V A N + IC, 1 M P G N ) were ~eated with P, 1 mg/kg/day initially, followed by progressive tapering once i m p r o v e m e n t in G F R was well established. Mean serum creatinine (SCr) (mg/dl): Pre-B 2wks 4wks 8 wlcs Post-B 6.5 4.4 3.2 2.8 In most pts, responsiveness to B was apparent within 2 wks. Three pts have had stable improved SCr for 8, 12 and 16 rues. Where data available, there has been no increase in viral load during P B. Four pts developed p n e u m o n i a during 8, causing death in one and progression to E S R D with stopping P in two. One pt died from A I D S 2 months after P stopped (5 rues. after c o m i n g off dialysis with P B). Conclusion: P B can reverse acute renal failure and delay ESRD in the short term, but infectious complications remain problematic. Some pts (unpredictably) appear to experience more sustained long-term benefit.
d. Undberq, Ochs.Cl. N.O. LA, Steven Smith*, Pennington Biomed Res.Ctr. B.R. LA, F. Husserl, J. Ross, A. Marquez-Julio, J. Figueroa, A. Walker, J. Naquin*, A. Burshell, J. Copley, Ochs. CI. N.O. LA. A prospective study was conducted in 39 CRF PTS (19 [M] and 20 [F]), with GFR <10 cc/min. We measured PRL, FSH, estrogen (E2), free testosterone (FT)
at baseline (BL) pdor to EPO admin, and at 3 and 6 months post EPO admin. In addition, DEXA measurements were obtained at
lumbar (L), femoral neck (FN) and radial (R) sites at BL. T scores (variability in BD compared to young normals) were compared between predial pts and pts on HD. Pts were divided into 2 grps based on their BL PRL <20 ng/ml (normal =6-20 ng/ml), vs. PRL • 20 ng,/ml. PRL > 20 PRL < 20 Hemodialysis (HD)
ON HD PRE 4 9 Gender M age 64 _+ 15 M F F aoe 53 + 14 4 9
Hypogonadal (HG) (FSH >40 mlu/ml or E <20 pg/ml or Free T <21 ng,/dl)
+ HG 5
-HG 8
ON HD (~ M 16
PRE 20 F
+ HG
10 HG
19
7
PREHDN= ONHDN= P 0.07 - 1.05 0.04 Lumbar (N =25) + 1.11 - 0.17 0.08 Radial (N=25~ + 0.15 - O.4O NS Paired T test showed no sig diff between PRL levels drawn at BL vs 3 mos & 6 mos after EPO admin. There was a sig diff in T score of the FN and LS at BL between pts predial & pts receiving HD. We conclude that the incidence of hyperprolactinemia is rare in pts with GFR <10 cc/min & that there is no sig elf of EPO on PRL or HG in this study. BD of FN & LS is sig less in pts on HD compared to 10Is predial. HG is common in pts with GFR <10 cc/min. Femoral Neck (N=17)
1997 SPRING CLINICAL N E P H R O L O G Y MEETINGS
21
23
IMPROVEMENT IN SERUM CREATININE LEVELS FOLLOWING RENAL ARTERY ANGIOPLASTY IN ELDERLY PATIENTS WITH ISCHEMIC NEPHROPATHY. Ronit H. Lavie. Jaime F. Avecillas, Frank E. Vogel, Daniel J. Javit, Richard Chart, Michael F. Michelis, Nephrology Section, Dept. of Medicine, Lenox Hill Hospital, New York, New York. Intervention for renal artery stenosis, which may cause iscbemic nephropathy and chronic renal failure, is increasingly common. We reviewed our experience in nine patients with angiographically proven renal artery stenosis who underwent pereutaneous transluminal renal artery angioplasty (PTRA) +/- stent placement. The indications included worsening renal function in all subjects, and refractory hypertension in 1/9. Data from these elderly patients included serum creatinine (Cr), Cr upon discharge, and followup Cr obtained 13+4 months following the procedure. Additionally, mean arterial blood pressure (MAP), plasma renin activity (PRA), and serum aldosterone (Aldo) levels were recorded. The mean data + SEM are shown below.
EFFECTS OF ISOFLURANE (ISF) ON RENAL PROXIMAL TUBULAR CELL ENERGETIC& Karen Lochhead Evan Klmmsch and Richard A. Zager. University of Washington Medical Center, Seattle, Wasldngton The post-operative period is a common clinical setting for the onset of acute tubular necrosis (ATN). ISF, a widely used fluorinated anesthetic, could potentially be a risk factor for ATN if it were shown to have direct nephrotoxic effects. ISF is metabolized to release inorganic fluoride, which is known to inhibit Na,K-ATPase and thus cause derangements in cellular energetics. The goal of this study was to examine the effects of ISF on cellular energetics using isolated rat proximal tubular segments (ITS). PTS were incubated with 0-7 mM doses of ISF, (overlapping with low mM ISF blood levels observed in humans undergoing ISF anesthesia). Adenine nucleotide levels were assessed alter a l hour incubation. Similar studies were done with sodium fluoride (NaF, 0.5-10 raM). To investigate whether changes in ATP were due to increased consumption by Na,K-ATPase, adenine nucleotides were measured in PTS incubated with ISF in the presence and absence of ouabain. To determine if the changes in ATP were due to an increase in aerobic metabolic work, oxygen consumption was measured in PTS incubated with ISF and ouabain. ISF induced striking dose dependent declines in cellular ATP (96% loss of ATP at the 7 mM dose) and the decrement in ATP occurred prior to substantial lethal cell injury as measured by LDH release. NaF caused significant reductions in the ATPIADP ratio at all concentrations tested. Onabain exerted no protection over the ISF induced decline in ATP, indicating timt an increase in Na,K-ATPase activity was not the mechanism of ATP loss. Oxygen consumption declined in the presence of ISF with no further decline seen with the addition of ouabain, indicating that ISF inhibited Na,K-ATPase driven respiration. In conclusion: (1) ISF causes a profound derangement in cellular energetics marked by a decline in cellular ATP which is likely a result of decreased ATP production. (2) These decrements in ATP can be reproduced using NaF, indicating that fluoride is the probable mediator of ISF-induced tubular injury. (3) ISF inhibits Na,Ko ATPase, which may contribute to the drug's cytotoxic effects.
age peak Cr discharge Cr followup Cr MAP pre-precedure MAP discharge PRApre-procedure Aldo pre-procedure
70+_4 yrs 4.2+0.8 mg/dl 2.9+0.7 mg/dl (p=0.06) 3.0+1.1 mg/dl 124+8 mmHg 100_+4 mmHg 8.5+2.5 ng/ml/hr 19.8+5.2 ng/dl
Complications included pseudoaneurysm at the femoral puncture site in 3/9 subjects. In summary, intervention improved serum Cr in our patients with ischemie nephropathy. Most benefit was observed when renal function was mildly to moderately decreased.
22
24
EFFECTS OF ERYTHROPOIETIN (EPO) ON PROLACTIN (PRL) LEVELS, HYPOGONADISM (HG) AND BONE DENSITY (BD) IN PATIENTS (PTS) WITH CHRONIC RENAL FAILURE (CRF)
P R E D N I S O N E (P) T R E A T M E N T O F HIVASSOCIATED GLOMERULOPATHIES: A T H E R A P E U T I C D I L E M M A : Suresh Mathew, Michael Choi, Paul J. Scheel, Jr., and W i l l i a m A. Briggs. The Johns Hopkins University School of Medicine, Baltimore, MD. Since the reports by Smith et al (Am. J. Med. 97:145 and 101:41), we have treated selected HIV seropositive patients (pts) with renal failure associated with glomerular diseases, predominantly HIV-associated nephropathy (HIVAN), with P. Current infection, ongoing IV drug abuse, psychiatric disease and non-compliant behavior precluded treatment (B). Ten pts (8 H I V A N , 1 H I V A N + IC, 1 M P G N ) were ~eated with P, 1 mg/kg/day initially, followed by progressive tapering once i m p r o v e m e n t in G F R was well established. Mean serum creatinine (SCr) (mg/dl): Pre-B 2wks 4wks 8 wlcs Post-B 6.5 4.4 3.2 2.8 In most pts, responsiveness to B was apparent within 2 wks. Three pts have had stable improved SCr for 8, 12 and 16 rues. Where data available, there has been no increase in viral load during P B. Four pts developed p n e u m o n i a during 8, causing death in one and progression to E S R D with stopping P in two. One pt died from A I D S 2 months after P stopped (5 rues. after c o m i n g off dialysis with P B). Conclusion: P B can reverse acute renal failure and delay ESRD in the short term, but infectious complications remain problematic. Some pts (unpredictably) appear to experience more sustained long-term benefit.
d. Undberq, Ochs.Cl. N.O. LA, Steven Smith*, Pennington Biomed Res.Ctr. B.R. LA, F. Husserl, J. Ross, A. Marquez-Julio, J. Figueroa, A. Walker, J. Naquin*, A. Burshell, J. Copley, Ochs. CI. N.O. LA. A prospective study was conducted in 39 CRF PTS (19 [M] and 20 [F]), with GFR <10 cc/min. We measured PRL, FSH, estrogen (E2), free testosterone (FT)
at baseline (BL) pdor to EPO admin, and at 3 and 6 months post EPO admin. In addition, DEXA measurements were obtained at
lumbar (L), femoral neck (FN) and radial (R) sites at BL. T scores (variability in BD compared to young normals) were compared between predial pts and pts on HD. Pts were divided into 2 grps based on their BL PRL <20 ng/ml (normal =6-20 ng/ml), vs. PRL • 20 ng,/ml. PRL > 20 PRL < 20 Hemodialysis (HD)
ON HD PRE 4 9 Gender M age 64 _+ 15 M F F aoe 53 + 14 4 9
Hypogonadal (HG) (FSH >40 mlu/ml or E <20 pg/ml or Free T <21 ng,/dl)
+ HG 5
-HG 8
ON HD (~ M 16
PRE 20 F
+ HG
10 HG
19
7
PREHDN= ONHDN= P 0.07 - 1.05 0.04 Lumbar (N =25) + 1.11 - 0.17 0.08 Radial (N=25~ + 0.15 - O.4O NS Paired T test showed no sig diff between PRL levels drawn at BL vs 3 mos & 6 mos after EPO admin. There was a sig diff in T score of the FN and LS at BL between pts predial & pts receiving HD. We conclude that the incidence of hyperprolactinemia is rare in pts with GFR <10 cc/min & that there is no sig elf of EPO on PRL or HG in this study. BD of FN & LS is sig less in pts on HD compared to 10Is predial. HG is common in pts with GFR <10 cc/min. Femoral Neck (N=17)