METASTATIC RENAL CARCINOMA

RCC develops from the proximal tubule cells!

If it hasn't metastasized then there is a 2/3 chance of survival at 5 years.

It is resistant to chemo and radiotherapy, so the only things that work are immunotherapy, "cytoreductive nephrectomy", tyrosine kinase inhibition and VEGF-inhibition because this prevents angiogenesis.

RENAL ULTRASOUND FOR KIDNEY STONES

Ultrasonography has become increasingly important technology for the detection of renal calculi. The sensitivity of ultrasonography is slightly superior to that of plain abdominal films. The renal calculi are detected by their marked echogenicity and associated acoustic shadowing. The minimal size of calculus that are detected or identified is at least 0.5 cm. with a transducer between 2.25 and 3.5 MHz. Transducers in the range of 6 - 10 MHz are able to detect renal calculi as small as 3 mm.

Normal kidney. Longitudinal section of the kidney (yellow arrowheads). The renal sinus is seen as an echogenic central zone. The cortex of the kidney is hypoechoic.

Renal ultrasonography is another imaging modality, which offers anatomical details of anatomical details without exposure to radiation or contrast material. The protection of the renal calculus is based on the presence a of highly echogenic focus with posterior acoustic shadowing of the stone. Renal ultrasonography is a useful screening tool for the demonstration of renal stones and evaluation of hydronephrosis in patients with suspected renal calculi. In most institutions, ultrasound for the detection of renal calculi is useful for patients where intravenous contrast or radiation is contraindicated. However, ultrasound is seldom utilized in the initial evaluation of patient with flank pain.

Renal calculus. Renal ultrasound demonstrating echogenic focus (red arrow) with an associated acoustical shadow (yellow arrowheads).

Advantages of Ultrasound

1. Good anatomical detail of the kidney in a short period of time.
2. No exposure to radiation.
3. No use of intravenous contrast agents.
4. Ultrasound is regarded as safe in obstetric patients.

Disadvantages of Ultrasound

1. Poor visualization of calcifications or obstructing stones in the ureter.
2. Lack of assessment of renal function.
3. The need for a full bladder to properly visualize stones at the ureteral vesicle junction (UVJ).
4. Limited role in the diagnosis of other pathology in the absence of a ureteral calculus.

EFFECT OF VITAMIN D ON URINARY CALCIUM

Vitamin D Repletion Does Not Alter Urinary Calcium Excretion in Healthy Postmenopausal Women - Abstract

Friday, 29 May 2009

Departments of Urology and Medicine, Osteoporosis Clinical Center and Research Program, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. To evaluate, in a posthoc analysis of a previous study, whether vitamin D repletion in postmenopausal women with insufficient vitamin D increases urinary calcium excretion, as vitamin D therapy might contribute to hypercalciuria and calcium stones in susceptible individuals, and the effect of vitamin D on the risk of urolithiasis warrants attention. We recruited 18 women at >/=5 years after menopause who had vitamin D insufficiency (serum 25(OH)-vitamin D, 16-24 mg/dL). We excluded women with a history of urolithiasis and kidney disease. Women had one calcium absorption study when vitamin D-insufficient, received vitamin D therapy, and completed a second calcium absorption study when vitamin D-replete. We fed subjects meals that mirrored the nutrient composition from self-reported 7-day diet diaries. To measure calcium absorption, we collected urine for 24 h during both visits. We achieved vitamin D repletion in all women (25(OH)-vitamin D before and after treatment, 22 and 63 mg/dL, respectively; P < style="font-weight: bold;">Calcium excretion did not change after vitamin D therapy (212 before vs 195 mg/day after; P = 0.60). Of four women with hypercalciuria (>247 mg/day), calcium excretion decreased in three (377-312 mg/day, not significant). Vitamin D supplementation did not increase the urinary calcium excretion in healthy postmenopausal women. Many stone formers are at risk of premature bone loss, vitamin D insufficiency, or both. Based on the present results we suggest a study of patients with hypercalciuria and nephrolithiasis to determine the risks of vitamin D therapy. Written by: Penniston KL, Jones AN, Nakada SY, Hansen KE. Are you the author? Reference: BJU Int. 2009 Apr 15. Epub ahead of print.

MARKERS OF KIDNEY FUNCTION

GFR is the speed of flow of the fluid that has been filtered through the kidney.

Creatinine Clearance is the volume of blood that is cleared of creatinine over a set time period.

To calculate both, you need to measure how much creatinine is in blood and urine at the same time.

The actual calculations are:

Creatinine clearance (C_Cr) can be calculated if values for creatinine's urine concentration (U_Cr), urine flow rate (V), and creatinine's plasma concentration (P_Cr) are known. Since the product of urine concentration and urine flow rate yields creatinine's excretion rate, creatinine clearance is also said to be its excretion rate (U_Cr×V) divided by its plasma concentration. This is commonly represented mathematically as

Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour produces 60ml of urine with a creatinine concentration of 1.25 mg/mL.

Commonly a 24 hour urine collection is undertaken, from empty-bladder one morning to the contents of the bladder the following morning, with a comparative blood test then taken. The urinary flow rate is still calculated per minute, hence:

To allow comparison of results between people of different sizes, the C_Cr is often corrected for the body surface area (BSA) and expressed compared to the average sized man as mL/min/1.73 m². While most adults have a BSA that approaches 1.7 (1.6-1.9), extremely obese or slim patients should have their C_Cr corrected for their actual BSA.

BSA can be calculated on the basis of weight and height.

KIDNEY STONES

The majority of kidney stones are calcium oxalate and calcium phosphate stones. 

Calcium oxalate stones form if there is excess calcium or oxalate in the urine.

Vitamin D will keep calcium urine levels lower.

Dietary calcium will keep urinary oxalate levels lower by not allowing oxalate to be absorbed from the intestines.

So, if the question comes up of whether one can give calcium supplementation to someone who has had renal stones then an approach might be the following:

1. Check for oxalate and calcium phosphate crystals in the urine - if present - don't start calcium supplementation.

2. Check for urinary supersaturation - if present - don't start calcium supplementation.

3. Perform a 24 hour urine collection to look for the the calcium and oxalate levels. The urinary calcium level should not be higher than 200-250mg/day (6-6.25mmol/day). If it is, do not start calcium supplementation, the other option being to use a thiazide to lower urinary calcium.

The trouble with urinary calcium readings is that you need to do the collection three times, because findings are likely to be sufficiently different over those days to miss an important metabolic abnormality if only 1 or 2 collections are made.

If none of these are present, then one can start calcium supplementation in association with:

- making sure the urine stays alkaline (pH>7) because calcium phosphate stones cannot form in alkaline urine.

This is done by eating lots of fruit and vegetables, because because fruit and vegetables are rich in potassium and potassium leads to higher levels of a urinary alkalinizer called citrate. A recommended mixture is 120ml of lemon juice mixed into 2 litres of water and drunk over the course of the day as lemonade.

Cranberry juice is not a good source of citrate, and orange juice is one juce to avoid because it raises oxalate levels. For the same reason, care has to taken with Vitamin C supplementation because for every 1g of vitamin C over 500mg, the urinary oxalate excretion increases by at least 6mg/day.

No-one knows how high is too high for urinary oxalate levels, but they should probably not be over 45mg/day (0.5mmol/day). Higher levels probably mean a higher chance of calcium oxalate stone formation.

- switching to a potassium-based salt. Indeed, even merely cutting your daily salt intake to 6g of salt/day (100mEq of sodium/2.3g of sodium) will lead to lower levels of calcium in the urine because the calcium will be absorbed by the body from the urine. This means less chance of kidney stones AND osteoporosis.

- switching to a low protein diet. 


The major inhibitor of calcium stones is citrate. Citrate supplementation can be done effectively with potassium-magnesium-citrate. Citrate supplementation will also make the urine more basic and therefore help decrease the potential to form stones. Citrate is present in citrus fruits. Four ounces of lemon juice mixed with 2 liters of water has been shown to increase urinary citrate levels. So feel free to indulge in healthy lemonade all year round, but go easy on the added sugar.
A major promoter of calcium stones is increased urinary oxalate. Much can be done to address this. First, a low-oxalate diet is important. Foods high in oxalate include: beer, chocolate milk, hot cocoa, tea, nuts, sesame and sesame butter or tahini, soy nut butter, strawberries and other berries, lemon peel, lime peel, and orange peel, purple or concord grapes, red currants, rhubarb, wheat germ and bran, beets and beet greens, dandelion, escarole, parsley, Swiss chard, watercress, or spinach, and many others. The Hoffman Center will guide you through this daunting dietary minefield and help to arrange for a healthy low oxalate diet.
Also, there must be enough dietary calcium in the diet. Yes, we actually encourage patients to have an adequate supply of calcium in their diets even if they have calcium kidney stones! One needs calcium to bind to the oxalate in order to prevent stones. If dietary calcium is low, then more oxalate is available to be excreted through the urinary tract to form calcium oxalate stones. So a seeming paradox actually makes sense.
Can I continue taking my vitamin C? Being that vitamin C is metabolized to oxalate, some prior studies have demonstrated a link between vitamin C supplementation and calcium oxalate stone formation. The largest study of this sort, part of the Nurses' Health Study, entitled "Intake of Vitamins B6 and C and the Risk of Kidney Stones in Women" which analyzed over 85,000 women, found no increased risk of stone formation with vitamin C intake. So, yes, our patients can continue their moderate dose vitamin C supplementation.
Vitamin B6 reduces urinary oxalate excretion and can increase urinary excretion of citrate. A research paper in the Journal of the American Society of Nephrology entitled "Intake of Vitamin B6 and the Risk of Kidney Stones in Women," was conducted to examine the association between the intakes of vitamins B6 and vitamin C and risk of kidney stone formation in 85,557 women with no history of kidney stones. It concluded that a high intake of vitamin B6 was inversely associated with risk of stone formation and that routine restriction of vitamin C to prevent stone formation appears unwarranted.
Although you do not have to restrict your vitamin C, you do have to cut out the salt. A low sodium diet can help prevent calcium kidney stones. We help our patients to implement a low salt diet in the setting of kidney stones.
Calcium phosphate stones
Calcium phosphate stones do not occur as commonly as calcium oxalate stones. Therapy for calcium phosphate stones is similar to that of calcium oxalate stones. The one exception is with regard to high oxalate in the urine, which patients with calcium phosphate stones don't have, and therefore do not have to address. In addition, in contradistinction to calcium oxalate stones, these stones thrive not in acidic, but in basic conditions. Treatment is therefore acidification of the urine. This can be achieved through cranberry extract. A diet rich in whole grains has been shown to acidify urine, and contains little of the phosphorous plentiful in animal protein. Additionally, the bran in grains binds excess calcium before it concentrates in the kidneys. We prescribe our calcium phosphate stone patients a diet rich in whole unrefined grains, assuming they are not sensitive to gluten.