06-09-2018 LE introduction kidney function
Chronic kidney damage
10,6% of the Dutch inhabitants has
chronic kidney damage. This mostly
means a decreased function of the
kidney or that the kidney is ‘leaking’
protein. A lot of these people have
complication of other diseases as
diabetes mellitus and hypertension
(diseases which cause damage to the
blood vessels. Adiposity rises, and with
that, the amount of diseases which cause vascular damage and with that the chronic kidney damage.
Of this 10,6%, 87% has a moderate increased risk of kidney failure, 10% an increased risk and 3% a
strongly increased risk.
The largest group of chronic kidney damage is caused by
vascular damage. Other causes are primary renal disease,
which can be congenital or inflammatory, renal disease as
part of a systemic disease like SLE (lungs, joints),
intoxication (chemo and drugs) and infections. Some of
these causes can also lead to acute renal failure.
A lot of people with kidney disease have a form of
comorbidity. Also, there is more often comorbidity in
patients with chronic kidney disease than in patients
without chronic kidney disease.
The kidney are placed retroperitoneal in the abdomen.
The glomeruli originate from the a. renalis. The a. renalis branches into a tangle of vessels, which is
surrounded by the space of Bowman. The ‘urine’ side of the glomerulus contains podocytes. These
are connected to each other and hold molecules that should not be present in the urine, like protein.
When a patient presents with a renal disease with protein loss, the podocytes are almost always
The lis of Henle starts in the cortex and continues into the medulla. In the medulla is an osmotic
gradient, which is useful for the concentration of urine.
The kidney have a couple of important functions:
Removal of water-soluble waste products by glomerular filtration and tubular secretion.
Homeostasis of electrolytes, acid-base and body volume by glomerular filtration, tubular
secretion and tubular reabsorption.
Hormone production: renin, vitamin D and EPO
Filtration is pressure mediated. The pressure in the glomerulus is not as high as the original blood
pressure. The pressure in the glomerulus lays around 55mmHg. In Bowman’s space, the pressure is
around 15mmHg. The colloid osmotic pressure in the blood (counterpressure to keep the blood in
the vessels) is around 30mmHg. The remaining filtrationpressure is approximately 10mmHg. This
causes the blood from the afferent arteriole to push into Bowman’s space.
The amount of filtrate = the concentration in the afferent arteriole
(Pcr) * the filtration speed (GFR (mL/min))
The amount of excretion = the concentration in the urine (Ucr) *
urination speed (mL/min).
𝑈𝑐𝑟 𝑥 𝑉
Hereby: GFR =
Secretion and reabsorbtion
The blood vessel does not end at the glomerulus, but runs
across the tubular system. This causes molecules to be
transported back into the blood, but also makes it able for
molecules that are not filtered at the glomerulus to pass
into the urine. Molecules that get reabsorbed are
molecules like glucose and amino acids. Molecules that
are actively secreted are molecules that the body wants
to remove from its system like medication or drugs.
Transport processes for secretion and reabsorption require a lot of oxygen. A lot of ATP has to be
generated as an energy source to reabsorb all the sodium that your body does not want to lose. The
amount of oxygen needed to do this, is almost equal to the amount of reabsorbed sodium. The
kidneys are the most oxygen consuming organs in the human body.
06-09-2018 LE introduction kidney function
Chronic kidney damage
Secretion and reabsorbtion
Assessment of kidney function
Causes of renal dysfunction
Entry-questions educative test
1. What is the length and weight of a normal kidney
2. How are the functional units of the nephron called?
3. What is the name of the part of the nephron where filtration takes place?
4. In which part of the kidney are glomeruli located?
5. In which part(s) of the kidney are Henle’s loops located
6. Describe the collection and draining system of the urine from glomerulus tot toilet.
7. What is a podocyte and what is the main function of this cell type?
8. What is meant with the subendothelial and subepithelial side of the glomerular basement membrane?
04-09-2018 Self study assignment – kidney function
1. Which factors determine the renal excretion of a substance?
2. What are the requirements for a substance to be a suitable marker for the glomerular filtration rate (GFR).
3. Is there a substance that fulfils these criteria?
4. Does creatinine fulfil these requirements?
5. Are the clearance of urea and creatinine the same?
6. What is the value of the GFR in a healthy subject?
7. How is GFR regulated? What is the physiologic response to renal hypoperfusion?
In Harrison two forms of proteinuria are addressed: glomerular proteinuria and overload (or overflow) proteinuria. There is a third form of proteinuria called tubular proteinuria.
8. Make a table in which the mechanism and causes of the three forms of proteinuria are depicted.
9. The international working group ‘Kidney Disease Improving Global Outcomes’ (KDIGO) has designed a staging classification of chronic kidney diseases based on GFR and albuminuria. In which stage is a patient included with a GFR of 40ml/min and an alb...
10. What is the usefulness of such a classification?
11. In addition to its excretory function, the kidney produces several hormones. Name three hormones and their function.
06-09-2018 LE types of renal disease
Diagnosis of glomerular disorders
Immune mediated glomerulonephritis
Tubular interstitial nephritis
07-09-2018 Presentations kidney diseases
Granulomatosis with polyangiitis (GPA)
Lupus nephritis (SLE)
10-09-2018 SSA Clinical presentation of various renal diseases
1. What is estimated by the numerator of Cockcroft equation?
2. A 45 year old male, weighing 85 kg as a plasma creatinine of 110umol/L; Over a period of 24 hour he produces 2 litres of urine with a creatinine concentration of 7mmol/L. Calculate the endogenous creatinine clearance.
3. A 79 year old male is wheelchair-dependent as a result of a hemiparetic stroke. Is his endogenous creatinine clearance higher, lower or equal to the GFR estimated by the Cockcroft equation?
4. Describe common complaints, findings at physical examination and laboratory findings of patients presenting with a nephrotic syndrome, nephritic syndrome and acute renal failure.
5. Describe which histologic lesions can cause a nephrotic syndrome, nephritic syndrome and acute renal failure and describe for each lesion what diseases are associated with its occurrence.
6. A female patient of 19 years of age is referred by her gastro-enterologists because of an increased serum creatinine of 425umol/l and proteinuria of 0.2g/24 hours. Her previous history includes Crohn’s disease, which has been treated with corticost...
a. Calculate the estimated GFR
b. Which renal diseases could be the cause of the renal insufficiency?
c. What are causes of tubule-interstitial injury?
7. As GFR declines, clinical and laboratory abnormalities develop (uremic symptoms). These include hyperkalaemia, increased parathyroid levels, cardiovascular abnormalities, anaemia, neurologic disorders and gastro-intestinal disorders. Describe the p...
13-09-2018 LE Renal replacement therapy
Manifestations of end stage renal disease
Indications for renal replacement therapy:
14-09-2018 SSA Biomarkers in renal disease
1. What is the main shortcoming of serum creatinine as biomarker of renal function? What are potential reasons for this shortcoming?
2. Is the term specificity appropriately used in the 3rd line of the second column on p221? Is the term selectivity appropriately used in the 7th line of the second column on p223?
3. Most biomarkers that are summarized in Tables 1 and 2 are associated with a decline in eGFR (chronic kidney disease). Are there biomarkers which are associated with a specific type of renal injury?
4. Name four criteria which are relevant for a biomarker study.
5. In the second column on page 227, the authors state that ‘urinary proteome analyses require normalization’. What do they mean with this statement?
6. Why is it important to have reliable predictor of the disease course in membranous nephropathy?
7. Based on the paper of van den Brand et al., which predictor of prognosis would you prefer in patients with membranous nephropathy?
8. On page 1248, line 5, vd Brand et al. state that with the biomarkers they describe a subset of patients is still misclassified. Assume that you have a cohort of 100 patients of whom 50% has disease progression (see table 1) and that you have a biom...
20-09-2018 LE molecular diagnostic approaches in renal disorders
DNA vs. RNA
LE next generation sequencing in molecular diagnostics of renal disease
Article Heterogenous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppresion
Article Next-generation sequencing for research and diagnostics in kidney disease
Advances in sequencing approaches
Identifying causal mutations
Genetic testing in kidney disease
Next generation sequencing
Congenital anomalies of the kidney and urinary tract
Models of inherited kidney disease
IL Genetic laboratory diagnostics in kidney disease
Flow in the lab
Kidney genes package
05-10-2018 LE introduction pathology
Minimal change glomerulopathy
Focal and segmental glomerulosclerosis (FSGS)
Nephritic syndrome (glomerulonephritis)
Immune complex glomerulonephritis
Acute tubular necrosis/tubulopathy
04-10-2018 LE principles histopathological research
Identification and preparation
Morphology and several applications
Rubin’s pathology: The kidney
The glomerulus is the Renal filter
Glomerular Endothelial Cells
Tubules Comprise Most of the Nephron
The Juxtaglomerular Apparatus Secretes Renin and Angiotensin
The Interstitium Provides Structural Support
Nephritic (Glomerulonephritic) Syndrome
Anti-Glomerular Basement Membrane Glomerulonephritis
Antineutrophil Cytoplasmatic Autoantibody (ANCA) Glomerulonephritis
Diseases of Tubules and Interstitium
Acute Ischemic and Nephrotoxic Acute Tubular Injury Commonly cause AKI
Causes of Acute Renal Failure
05-10-2018 E-learning kidney
Histology and microscopy
Sclerosis, fibrosis and hyalinosis
LE Introduction to Clinical Chemistry and theoretical aspects of clinical chemistry
Accuracy and precision
Limit of detection (LOD) and limit of quantitation (LOQ)
Sources of variation
Total allowable error
Presentations of test characteristics
Carry over effect
It is also very important for the sodium concentration. Because sodium is very closely regulated in the body. It rarely changes. When it does, it is mostly pathogenic. So if there is carry-over, a healthy patient may be false diagnosed with a high sod...
Limit of detection (LOD)
Limit of quantitation (LOQ)