Differential renal function

Jackson B, McGrath BP, Matthews PG, Wong C, Johnston Cl. Differential renal function during angiotensin converting enzyme inhibition in renovascular hypertension. Hypertension 1986 8 650-654. 

A complete understanding of why specific metal complexes target certain tissues has yet to be achieved, but would be extremely valuable for the rational design of new radiopharmaceuticals. Complexes of 99mTc vvilli diphosphonates, e.g. methylenediphosphonate, localize in bone and especially in areas of disturbance of bone metabolism, such as tumours thus they may be used to map the presence and location of bony metastases from various types of cancer. Chelates such as "Tc-DTPA may be used to study differential renal function in the kidneys or to monitor the function of a transplanted kidney. Attachment of chelating groups, often based on DTPA, to antibody proteins permits the formation of Tc- or in-labelled antibodies for tumour localization. 

For each patient the key features derived from MR urography include calculation of differential renal function (both volume and Patlak) (vDRF and pDRF), signal versus time curves for each kidney and the aorta, individual kidney GFR index of each kidney, concentration and excretion from each compartment, renal and calyceal transit times and overall anatomic diagnosis. It is important to understand that we have two methods to determine the differential renal function one based on volume and one based on the individual kidney GFR as determined by the Patlak plot. In most cases these are symmetric however, when there is a difference in these two measures of DRF it implies a change in renal hemodynamics that may ultimately provide information about which kidneys will benefit from surgery. 

Dynamic renography allows estimation of three parameters of renal function blood flow to the kidney renal clearance (Prigent et al. 1999 Rutland 1985 PiEPSz et al. 1998), i.e., the extraction of a tracer from the blood, when estimation of relative clearance occurs as in differential renal function (DRF) and the drainage function or excretion from the kidney. 

Fig. 1.3.17. Differential renal function using Tc-99m DMSA and Tc-99m MAG3 in the same children. The studies were done within 4 weeks of each other. There is close correlation between the two tracers...

The best method to evaluate and to quantify obstruction is the radio-isotope study (diuretic radionuclide renogram). Two aspects of renal function are assessed renal clearance and excretion of the tracer. Estimation of relative clearance (differential renal function) requires the measurement of GFR by injection of chromium isotope-ethylnedi-amine-tetraacetic acid (Cr-EDTA) using a simple plasma sample technique. The most accurate method for evaluation of GFR is based on the plasma disappearance curve after a single bolus injection of a glomerular tracer. 

Diff funct, differential renal function of affected kidney PEE, pelvic excretion efficiency of affected kidney (see Chap. 1.1, Nuclear Medicine, for details of PEE)... 

Urea Pharmacokinetics. Pharmacokinetics summarizes the relationships between solute generation, solute removal, and concentration in a patient s blood stream. In the context of hemodialysis, this analysis is most readily appHed to urea, which has, as a consequence, become a surrogate for other uremic toxins in the quantitation of therapy and in attempts to describe its adequacy. In the simplest case, a patient is assumed to have no residual renal function. Urea is generated from the breakdown of dietary protein, accumulates in a single pool equivalent to the patient s fluid volume, and is removed uniformly from that pool during hemodialysis. A mass balance around the patient yields the following differential equation ... 

Monitoring Perform complete blood counts, including differential white cell count and liver function tests before starting sulfasalazine and every second week during the first 3 months of therapy. During the second 3 months, perform the same tests once monthly and, thereafter, once every 3 months and as clinically indicated. Also perform urinalysis and assess renal function periodically during treatment. 

Monitoring Periodic monitoring for toxicity, including CBC with differential and platelet counts, and liver and renal function testing is mandatory. Periodic liver biopsies may be indicated in some situations. Monitor patients at increased risk for impaired methotrexate elimination (eg, renal dysfunction, pleural effusions, ascites) more frequently (see Precautions). 

Renal function, urinalysis (especially serum creatinine and urine protein prior to each dose), and blood chemistry (to include serum uric acid, phosphate, and bicarbonate), white counts with differential during intravenous therapy... 

Blood pressure, heart rate, respiratory rate, CBCwith differential, and hepatic function. For those on long-term therapy, expect blood chemistry studies and hepatic and renal function tests to be performed periodically... 

Renal Effects. Occupational exposure to silver metal dust has been associated with increased excretion of a particular renal enzyme (N-acetyl-p-D glucosaminidase), and with decreased creatinine clearance (Rosenman et al. 1987). Both of these effects are diagnostic of marginally impaired renal function. However, the workers in this study were also exposed to cadmium, which was detected in the urine of 5 of the 27 workers studied. Cadmium is known to be nephrotoxic differentiation of the effects of the two metals in the kidney is not possible with the data presented. Therefore, no conclusion can be drawn regarding renal effects of silver based on this study. 

Carvounis CP, Nisar S, Guro-Razuman S (2002) Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int 62 2223-2229 Dunn SR, Qi Z, Bottinger EP et al. (2004) Utility of endogenous creatinine clearance as a measure of renal function in mice. Kidney Int 65 1959-1967... 

Stoll PM, Stokes PE, Okamoto M. Lithium isotopes differential effects on renal function and histology. Bipolar Disord 2001 3(4) 174-80. 

Acute ciclosporin-induced nephrotoxicity, causing reduced renal function, develops within the first month, and includes a dose-related rise in serum creatinine concentrations and hyperkalemia. Fatal acute tubular necrosis has also been noted after very high intravenous doses (SEDA-19, 345). Although it is clinically often difficult to differentiate from acute allograft rejection in renal transplant patients, the alteration in renal function promptly resolves on ciclosporin withdrawal or dosage reduction, and initial acute renal insufficiency is not clearly associated with the development of subsequent chronic renal dysfunction (93). Several conditions, such as pre-existing hypovolemia, concomitant diuretic treatment, or renal artery stenosis, are susceptibility factors. 

Various arylpropionic acids show similar specificity. For most, if not all, the (5) enantiomer is the pharmacologically active one, whereas the R) enantiomer is usually much less active, although the ratio of iS)/ R) activity varies from drug to drug (and species to species). Only one of these drugs, however, is administered as the separated (S) enantiomer (naproxen, Naprosyn ). Normally these drugs are considered safe, and one cannot readily differentiate between the relative activities of the (S) and (R) forms because the in vivo half-life is very short, typically one or two hours. In patients with impaired renal function, where clearance is much slower, however, problems can arise. From in vivo studies of ibuprofen, it was established that the (S)-(-l-) isomer was responsible for antiinflammatory activity. In vivo, however, the (/ )-(-) isomer may become active because there is stereoselective inversion from R) to (S) (but not from 5 to R) in vivo with a half-life of about two hours. This inversion apparently proceeds by stereoselective formation of the coenzyme A (CoA) ester of the (f )-(-)-arylpropionic acid, followed by epimerization and release of the (S)-(+)-enantiomer. This epimerization is observed in vivo before the oxidative metabolism. Such inversion from (R) to (S) in vivo is also known for fenoprofen and benoxa-profen, and is expected to occur for most of the drugs of this series. ... 

Much of the evidence, however, is based on prolonged plasma half-lives of drugs that are metabolized totally or mainly by hepatic micrasomal enzymes (e.g antipyrine, phenobarbital, acetaminophen). In evaluating the effect of age on drug metabolism, one must differentiate between normal" loss of enzymatic activity with aging and the effect of a disea.sed iiver from hepatitis, cirrhosis, etc., plus decreased renal function, becau.se much of the water-soluble conjugation products are excreted in the liver. 

Narayanan K et al (2013) Human embryonic stem cells differentiate into functional renal proximal tubular-like cells. Kidney Int 83(4) 593-603... 

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