Simon M. Gruenewald

PREDICTING GLOMERULAR FILTRATION RATE AFTER KIDNEY TRANSPLANTATION

Serum creatinine is an important clinical measure of impairment of glomerular filtration rate (GFR) after kidney transplantation. The use of formulas that predict GFR (such as the Cockcroft-Gault) derived from patients with chronic renal failure and standardized against measured creatinine clearance may not be accurate when applied to kidney transplant recipients. The purpose of this study, was to investigate the level of inaccuracy and its causes and then to derive predictive GFR formulas that are appropriate to renal transplantation. Determinants of isotopic GFR, serum creatinine, and muscle mass were evaluated in consecutive kidney recipients (n = 146) using 99mTc DTPA GFR (n = 751) as a reference method. Factors that predicted GFR apart from serum creatinine included sex, height, body weight, serum urea, years on dialysis, numbers of rejections and infective episodes, and prednisolone dose. The relationship between serum creatinine and GFR was highly variable and dependent on factors that alter muscle mass and muscle catabolic rate. The relationship was further altered by ATN and chronic rejection when tubular secretion of creatinine was reduced. Three alternative GFR formulas (which can be applied to renal transplant patients according to the availability of clinical parameters) were derived and tested against six published methods of GFR estimation. Our derived formulas had the highest correlation, no overall bias, least scatter of sum of squares, and least error at low levels of GFR. They represent a better estimation of GFR in kidney transplantation than published formulas, and would allow a standardized approach to the study of long-term renal dysfunction.

Oral cyclosporine but not tacrolimus reduces renal transplant blood flow.

Background. Calcineurin inhibitors are important immunosuppressive agents, but cause nephrotoxicity. Methods. Instantaneous intra-renal transplant hemodynamics were assessed in 22 patients using quantitative cineloop color Doppler imaging after dosing with microemulsion cyclosporine (CSA) or tacrolimus (TAC). Results. CSA dosing resulted in renal hypoperfusion, with a mean relative reduction of 43%±20% (range 22–76%) in maximal fractional area (MFA) of color pixels to nadir, compared to baseline. The mean effect occurred 1.1±0.9 hr (median 1 hr) after CSA dosing and was abrogated by calcium channel blockers (P <0.05). The main renal artery velocities, resistive index and small vessel perfusion were unchanged, suggestive of medium-sized arteries mediated vasoconstriction. In contrast, TAC did not alter renal vascularity (2.3±4.0% absolute reduction of MFA color pixels vs. 10.7±6.5% with CSA, P <0.01). Conclusion. CSA, but not TAC, induces phasic hypoperfusion of variable severity within small to medium sized intra-renal arteries soon after dosing, mitigated by calcium channel blockade.

Comparative assessment of techniques for estimation of glomerular filtration rate with 99mTc-DTPA.

The relative accuracy of five simplified methods of measuring glomerular filtration rate was prospectively assessed using 99mTc-DTPA. The slope of the biological clearance curve, the 3-h volume of dilution and three renal tracer uptake methods (Piepsz, Gates and Nielsen) were concurrently compared with a multiple blood sampling reference method. The volume of dilution method from a single blood sample was markedly superior to the other four simplified methods which all had a similar degree of accuracy.

Kidney Depth Measurement and Its Influence on Quantitation of Function from Gamma Camera Renography

Both total and relative renal function assessed from gamma camera renography are influenced by the depths of the kidneys in the body. Despite the ease with which renal depths may be measured (by ultrasound or nuclear medicine lateral scans), when calculating the total uptake function it is common practice to estimate the renal depth from the patients weight-to-height ratio. Furthermore, it is often assumed that there is no significant effect on relative function measurements due to different depths of right and left kidneys. Our data, from 150 consecutive patients, does not support this assumption or the use of calculated depth estimates and highlights the need for accurate kidney depth measurement.

Diagnosis of kidney transplant obstruction using Mag3 diuretic renography

Kidney transplant obstruction (KTO) following renal transplantation remains an important reversible cause of allograft dysfunction, requiring prompt diagnosis to prevent long‐term graft damage. Although ultrasound can accurately diagnose renal transplant hydronephrosis, it cannot be used to assess its functional significance. We prospectively assessed the utility of technetium‐99m mercaptoacetyltriglycine (Tc99m MAG3) diuretic renography for the diagnosis of allograft KTO, using standard visual and quantitative parameters, as well as calculated renal output efficiency (OE), which has been postulated to improve diagnostic yield. From a cohort of 45 renal transplant patients, two subgroups were formed. The first group of transplant recipients (n=21) with stable function and no obstruction was used to derive normal values for Tc99m MAG3 scans. A second group of transplant recipients with acute renal dysfunction in whom KTO was clinically suspected was used to test the diagnostic utility of these derived values (n=43 scans). KTO was diagnosed independently of the MAG3 scans by a fall in the serum creatinine in response to renal pelvis urinary drainage. OE in 12 renal allografts with KTO was significantly reduced compared with 31 Tc99m MAG3 scans without KTO (59.6±18.9 vs. 81.6±5.4%, p<0.001). In KTO, the mean time of isotope appearance in the bladder (time to bladder [TTB]) was extended compared with unobstructed allografts (7.9±4.1 vs. 3.6±1.5 min, p<0.001). Measurement of OE significantly improved the accuracy of diuretic MAG3 renography in the diagnosis of renal allograft KTO, especially when supplemented by the TTB, parenchymal transit time and shape of the renogram curve. Ureteric obstruction of the kidney transplant can be diagnosed with an OE reduced to <75% (sensitivity 92%, specificity 87%) and confirmed by isotope hold‐up in the pelvicalyceal system. A normal or slowly declining renogram curve effectively excluded KTO (sensitivity of 96%, negative predictive value of 84%). A parenchymal transit time of >5 min and a TTB of >7 min both yielded a sensitvity of 92% and a specificity of 81%. In conclusion, MAG3 renography is a clinically useful investigation for the diagnosis of KTO.

Detection of chronic allograft nephropathy by quantitative doppler imaging.

Background. Chronic allograft nephropathy (CAN) is the major cause of graft loss, and early detection is desirable to avoid irreversible graft damage. We have evaluated a new technique of color Doppler quantification using Cineloop (Philips Medical Systems, Bothell, WA) imaging for noninvasive diagnosis of CAN. Methods. Provisional normal ranges were defined by pilot study (n=13) and prospectively tested in stable recipients in whom CAN was independently quantified by contemporaneous histology (n=67), using the Banff schema. Results. The maximal fractional area (MFA, systolic color pixels/total area) was 28.7±9.7% in normal subjects and reduced to 18.8±8.0% in grade 1 and 12.5±6.4% in grade 2 CAN (both P <0.001). The minimum color fractional area was reduced from 10.3±5.3% in normal subjects to 3.1±2.6% in grade 2 CAN (P <0.001), but was less useful. Distance from peripheral color pixels to capsule increased in CAN grade 2 versus 0 (6.0±1.6 vs. 3.9±1.0 mm, respectively;P <0.001). Calcineurin inhibitor nephrotoxicity reduced MFA (18.0±9.3 vs. 26.9±10.7%;P <0.001) and other dynamic measurements. Parenchymal damage exerted minimal effect on resistance index, mean variance, and peak Doppler velocity. MFA (cutoff<17.3%) can diagnose CAN (sensitivity 69%, specificity 88%, positive predictive value 86%) and severe CAN (sensitivity 87%, specificity 71%, negative predictive value 95%). Distance to capsule >5 mm was less sensitive (49%) but more specific (91% alone, and 97% combined with MFA). Conclusions. In conclusion, quantitative Doppler ultrasound can reliably detect CAN and, although imperfect at correctly grading, allows recognition of significant tubulointerstitial damage for initiation of a confirmatory needle core biopsy.

Colour duplex ultrasound accurately identifies focal stenoses in dysfunctional autogenous arteriovenous fistulae

Aims:  The aims of this study is to correlate colour duplex ultrasonography (US) with contrast fistulography for the detection of functional stenoses in the autogenous AVF (arterio‐venous fistula) circuit.

Defining a Significant Stenosis in an Autologous Radio‐Cephalic Arteriovenous Fistula for Hemodialysis

The current definition of a significant stenosis in an autologous arteriovenous fistula (aAVF), the percentage narrowing compared with the adjacent “normal” vessel, is inaccurate. We believe a significant stenosis in the aAVF is an absolute minimal luminal diameter determined by the requirements of the hemodialysis pump. To determine what absolute diameter constitutes a hemodynamically significant stenosis in a radio‐cephalic autologous arteriovenous fistula (RC aAVF), the minimal luminal diameter of dysfunctional RC aAVF was compared to that of functional RC aAVF using grayscale and color ultrasound. There were 93 fistulas in study group and 77 in control group. The mean minimum luminal diameter in study group was significantly lower than in control group (2.19 vs. 4.71 mm, p 0.001). With a cutoff value of 2.7 mm, there was 90% sensitivity and 80% specificity in distinguishing functional fistula from dysfunctional fistula. The area under the receiver–operator curve was 90% (CI 84–94%), indicating that a 2.7 mm diameter is accurate in discriminating functional from dysfunctional fistulas. An absolute minimal luminal diameter of 2.7 mm, as determined with grayscale and color ultrasound, is a useful cutoff for defining significant stenosis in a RC aAVF.

Low-dose dopamine after kidney transplantation: assessment by Doppler ultrasound.

Low‐dose dopamine (LDD) is commonly used after kidney transplantation as a renoprotective agent, although the benefits of dopamine (DA) in this setting are controversial. LDD increases renal blood flow, decreases resistive index (RI) and causes diuresis in normal kidneys. We hypothesised that the vasculature of a denervated renal transplant may not respond to DA in the same way as healthy native kidneys. In a prospective, controlled study, renal blood flow velocity and vascular resistance were measured by Doppler ultrasound in recent kidney transplants (n=20) over a range of DA doses (0–5 μg/kg/min). Main renal artery velocity was lower in kidneys with acute renal dysfunction than in those with normal function (0.60±0.31 vs. 0.81±0.24, respectively, p<0.05). There was no demonstrable haemodynamic effect of LDD on either RI or main renal artery velocity as measured by Doppler ultrasound. Interestingly, the only significant correlation with mean RI was trough cyclosporin A level (r=0.57, p<0.001). Technical or timing factors cannot be used to explain the absence of DA effect, with equivalent doses capable of producing vasodilatation and reduced RI in studies of normal kidneys. In summary, these findings contrast the DA response of healthy native kidneys and may explain studies showing no clinical benefit of LDD in the early post‐transplant period. These data suggest an insensitivity of recently implanted kidneys to the vasodilatory effects of LDD, that other factors such as cyclosporin A vasoconstriction may also be important, and question the rationale for routine LDD after kidney transplantation.

Mercaptoacetyltriglycine diuretic renography and output efficiency measurement in renal transplant patients.

Abstract Suspected urinary tract obstruction following renal transplantation presents a diagnostic dilemma. The purposes of this study were: (1) to establish a normal range of measurement of output efficiency (OE) in the renal transplant population, and (2) to assess prospectively the usefulness of OE in the setting of allograft obstruction. Twenty-two renal transplant patients with stable renal function and no evidence of hydronephrosis on serial ultrasound examination had a diuretic mercaptoacetyltriglycine scan with calculation of OE. Three renal transplant patients with confirmed graft obstruction were also studied. Standard qualitative and quantitative parameters as well as OE were calculated. The mean OE for the 22 normal renal transplant patients was 86.3%±3.7% (range: 77%–91%). OE values in the three obstructed patients were 59%, 68% and 75% respectively. It is concluded that OE should normally exceed 77% in renal graft recipients. OE is a promising means of diagnosing functional obstruction in these patients.