Question 1:
High creatinine level is usually due to decrease tubular secretion, Howver, there are other reasons that can lead to elevated creatinine level. These can be devided into 3 categories:
- Increased production of creatinine.
- Interference with the assay.
- Decreased tubular secretion of creatinine.
1) Increase production: Creatinine is produced in muscle by the nonenzymatic conversion of creatine and phosphocreatinine. The creatinine generated is proportional to muscle mass and is relatively constant.
Increased muscles breakdown can lead to increase creatinine release, this can happen in Rhabdo or intense exercise.
Fenofibrate can lead to high creatinine level, the mechanism is not well known but it is believed to be related to increase creatinine production.
An increase in serum creatinine can result from increased intake of protein and creatine supplements or increased ingestion of cooked meat (which contains creatinine converted from creatine by the heat from cooking).
2) Interference with the chemical method used to analyze serum creatinine. This can be influenced by some endogenous substances such as acetone and acetoacetate (such as in diabetic ketoacidosis), fasting and hemolysis. These will lead to overestimate the serum creatinine level.
Some medication such as cephalosporins (specifically cefoxitin and cefazolin) barbiturates; N-acetylcyteine; and some chemotherapeutic agents such flucytosine.
Another material known to give a false high creatinine level is nitromethane, the usual cause of high level creatinine with toxic alcohol ingestion.
3) About 15% of creatinine is secreted in the tubules. It is secreted by the organic cation secretory pump that can be inhibited by other organic cations. Trimethoprim and H2-blockers can inhibit this process and lead to falsely high serum creatinine.
Question 2:
The relation between urea level and creatinine level can be used as an indicator to identify the cause of renal failure. (Urea-creatinine ratio).
- Both urea and creatinine are freely filtered by the glomeruli. Urea gets reabsorbed by tubules through regulation, creatinine doesn’t get reabsorbed.
Urea – Creatinine ratio is calculated by dividing urea level/ creatinine level.
Urea x 1000/ creatinine ( urea is measured by mmol while creatinine is measure by micro mol.).
- Ratio more than 100 (>100/1) that is usually due to pre-renal causes (urea absorption increased compared to creatinine).
- Ratio between 40 – 100 that is either normal or post renal.
- Ratio 40:1 that is usually due to intrinsic renal damage (urea unable to be absorbed so it becomes like creatinine and the ratio will get closer to 1).
Back to our case, urea was 6.8, Creatinine was 172. So the ratio will be (6.8 x 1000/ 172) = 39.5 (less than 40).
Causes of decrease Urea-Creatinine ratio (SIMPLE SR)
- Severe liver dysfunction
- Intrinsic renal damage
- Malnutrition
- Pregnancy
- Low protein diet
- SIADH
- Rhabdomyolysis
Question 3,
Blood tests for this patient showed normal Full Blood picture (without eosinophilia), normal liver function with normal albumin level.
Urine microscopy showed WBC and RBC. That patient had normal U/S and maintained normal urine out put (between 50-80 ml/hr). Serum creatinine remained elevated.
That patient underwent renal biopsy that showed histopathological features consistent with acute tubulointerstitial nephritis (ATN)
This patient had Meth induced ATN. That patient was treated with prednisolone and Meth cessation.
Doctors/ people are becoming more aware of drugs induced ARF, the usual causes are rhabdomolysis and malignant high blood pressure (induced by intense arterial vasoconstriction). ATN is another reason.
There are increasing evidence that these cases respond to steroids or immunosuppressant and these can prevent the development of fibrosis and the permanent impairment in kidney function.