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The renal system consists of the kidney, ureters, and the urethra. The overall function of the system filters approximately 200 liters of fluid a day from renal blood flow which allows for toxins, metabolic waste products, and excess ion to be excreted while keeping essential substances in the blood. The kidney regulates plasma osmolarity by modulating the amount of water, solutes, and electrolytes in the blood. It ensures long term acid-base balance and also produces erythropoietin which stimulates the production of red blood cell. It also produces renin for blood pressure regulation and carries out the conversion of vitamin D to its active form. The renal development, the process of urine production and excretion, and the clinical significance of the renal system will be the focus of this article.

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Definition and classification of CKD Defining CKD. CKD is defined as abnormalities of kidney structure or function, present for a minimum of 3 months, with implications for health (Table 1).1 Classifying CKD. CKD is classified based on Cause, GFR category (G1–G5), and Albuminuria category (A1–A3), abbreviated as CGA.
1 These 3 components of the classification system are each critical in the assessment of people with CKD and help enable determination of severity and risk. Listed below are reference tables describing each component. Note that while the definition of CKD includes many different markers of kidney damage and is not confined to decreased GFR and albumin-to-creatinine ratio (ACR) >30 mg/g [>3 mg/mmol], the classification system is based on the 2 dimensions of GFR and degree of albuminuria (Tables 2 and 3). This nuance is often missed by healthcare providers and students.
It is well established that patient advocates with CKD and healthcare providers prefer the more clinically useful and generally understood assessment of GFR resulting from the use of GFR estimating equations compared with serum creatinine (SCr) alone. Globally, although still not universally available in all countries, SCr is measured routinely and the approach to assessment of GFR is therefore to use SCr and an estimating equation for initial assessment of GFR. The approach to evaluation of GFR using initial and supportive tests is described in greater detail in Chapter 1.
Etiology of CKD should be sought, and there are numerous systems for grouping various etiologies, some of which are evolving with new knowledge and diagnostic tools.
There are congenital and genetic causes of CKD, some associated with systemic diseases, and others that are primary. It is beyond our remit to suggest a specific approach, but we highlight the importance of establishing a cause to individualize management of CKD.

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1.1: DEFINITION OF CKD
1.1.1: CKD is defined as abnormalities of kidney structure or function, present for43 months, with implications for health. (Not Graded)
1.2: STAGING OF CKD
1.2.1: We recommend that CKD is classified based on cause, GFR category, and albuminuria category (CGA). (1B)
1.2.2: Assign cause of CKD based on presence or absence of systemic disease and the location within the kidney of
observed or presumed pathologic-anatomic findings. (Not Graded)
1.2.3: Assign GFR categories as follows (Not Graded):
1.2.4: Assign albuminuria* categories as follows (Not Graded):
*note that where albuminuria measurement is not available, urine reagent strip results can be substituted (Table 7)
1.3: PREDICTING PROGNOSIS OF CKD
1.3.1: In predicting risk for outcome of CKD, identify the following variables: 1) cause of CKD; 2) GFR category;
3) albuminuria category; 4) other risk factors and comorbid conditions. (Not Graded)
Criteria for CKD (either of the following present for 43 months)
Markers of kidney damage (one or more) Albuminuria (AER Z30 mg/24 hours; ACR Z30 mg/g [Z3 mg/mmol])
Urine sediment abnormalities
Electrolyte and other abnormalities due to tubular disorders
Abnormalities detected by histology
Structural abnormalities detected by imaging
History of kidney transplantation
Decreased GFR GFR o60 ml/min/1.73 m2 (GFR categories G3a–G5)
Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate.

Guideline 1.
Definition and Stages of Chronic Kidney Disease (p. S46)

Adverse outcomes of chronic kidney disease can often be prevented or delayed through early detection and treatment. Earlier stages of chronic kidney disease can be detected through routine laboratory measurements.

The presence of chronic kidney disease should be established, based on presence of kidney damage and level of kidney function (glomerular filtration rate [GFR]), irrespective of diagnosis.

Among patients with chronic kidney disease, the stage of disease should be assigned based on the level of kidney function, irrespective of diagnosis, according to the KDOQI CKD classification:

EVALUATION OF LABORATORY MEASUREMENTS FOR CLINICAL ASSESSMENT OF KIDNEY DISEASE (PART 5, p. S76)

The definition and staging of chronic kidney disease depends on the assessment of GFR, proteinuria, and other markers of kidney disease. The goals of Part 5 are to evaluate the accuracy of prediction equations to estimate the level of GFR from serum creatinine, the accuracy of ratios of protein-to-creatinine concentration in untimed (�spot�) urine samples to assess protein excretion rate, and the utility of markers of kidney damage other than proteinuria. As described in Appendix 1, Table 151, the Work Group evaluated studies according to accepted methods for evaluation of diagnostic tests. To provide a more comprehensive review, the Work Group attempted to integrate the systematic review of specific questions with existing guidelines and recommendations.

Guideline 4.
Estimation of GFR (p. S76)

Estimates of GFR are the best overall indices of the level of kidney function.

The level of GFR should be estimated from prediction equations that take into account the serum creatinine concentration and some or all of the following variables: age, gender, race and body size. The following equations provide useful estimates of GFR:

In adults, the MDRD Study and Cockcroft- Gault equations;
In children, the Schwartz and Counahan- Barratt equations.

The serum creatinine concentration alone should not be used to assess the level of kidney function.

Clinical laboratories should report an estimate of GFR using a prediction equation, in addition to reporting the serum creatinine measurement.

Autoanalyzer manufacturers and clinical laboratories should calibrate serum creatinine assays using an international standard.

Measurement of creatinine clearance using timed (for example, 24-hour) urine collections does not improve the estimate of GFR over that provided by prediction equations. A 24-hour urine sample provides useful information for:
Estimation of GFR in individuals with exceptional dietary intake (vegetarian diet, creatine supplements) or muscle mass (amputation, malnutrition, muscle wasting);
Assessment of diet and nutritional status;
Need to start dialysis.

Guideline 5.
Assessment of Proteinuria (p. S93)

Normal individuals usually excrete very small amounts of protein in the urine. Persistently increased protein excretion is usually a marker of kidney damage. The excretion of specific types of protein, such as albumin or low molecular weight globulins, depends on the type of kidney disease that is present. Increased excretion of albumin is a sensitive marker for chronic kidney disease due to diabetes, glomerular disease, and hypertension. Increased excretion of low molecular weight globulins is a sensitive marker for some types of tubulointerstitial disease. In this guideline, the term �proteinuria� refers to increased urinary excretion of albumin, other specific proteins, or total protein; �albuminuria� refers specifically to increased urinary excretion of albumin. �Microalbuminuria� refers to albumin excretion above the normal range but below the level of detection by tests for total protein. Guidelines for detection and monitoring of proteinuria in adults and children differ because of differences in the prevalence and type of chronic kidney disease.

Guidelines for Adults and Children:

Under most circumstances, untimed (�spot�) urine samples should be used to detect and monitor proteinuria in children and adults.

It is usually not necessary to obtain a timed urine collection (overnight or 24- hour) for these evaluations in either children or adults.

First morning specimens are preferred, but random specimens are acceptable if first morning specimens are not available.

In most cases, screening with urine dipsticks is acceptable for detecting proteinuria:

Standard urine dipsticks are acceptable for detecting increased total urine protein.

Albumin-specific dipsticks are acceptable for detecting albuminuria.

Patients with a positive dipstick test (11 or greater) should undergo confirmation of proteinuria by a quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio) within 3 months.

Patients with two or more positive quantitative tests temporally spaced by 1 to 2 weeks should be diagnosed as having persistent proteinuria and undergo further evaluation and management for chronic kidney disease as stated in Guideline 2.

Monitoring proteinuria in patients with chronic kidney disease should be performed using quantitative measurements.

Specific Guidelines for Adults:

When screening adults at increased risk for chronic kidney disease, albumin should be measured in a spot urine sample using either:
Albumin-specific dipstick;
Albumin-to-creatinine ratio.

When monitoring proteinuria in adults with chronic kidney disease, the protein to-creatinine ratio in spot urine samples should be measured using:
Albumin-to-creatinine ratio;
Total protein-to-creatinine ratio is acceptable if albumin-to-creatinine ratio is high (>500 to 1,000 mg/g).

Specific Guidelines for Children Without Diabetes:

When screening children for chronic kidney disease, total urine protein should be measured in a spot urine sample using either:
Standard urine dipstick;
Total protein-to-creatinine ratio.

Orthostatic proteinuria must be excluded by repeat measurement on a first morning specimen if the initial finding of proteinuria was obtained on a random specimen.

When monitoring proteinuria in children with chronic kidney disease, the total protein- to-creatinine ratio should be measured in spot urine specimens.

Specific Guidelines for Children With Diabetes:

Screening and monitoring of post-pubertal children with diabetes of 5 or more years of duration should follow the guidelines for adults.

Screening and monitoring other children with diabetes should follow the guidelines for children without diabetes.

Guideline 6.
Markers of Chronic Kidney Disease Other Than Proteinuria (p. S103)

Markers of kidney damage in addition to proteinuria include abnormalities in the urine sediment and abnormalities on imaging studies. Constellations of markers define clinical presentations for some types of chronic kidney disease. New markers are needed to detect kidney damage that occurs prior to a reduction in GFR in other types of chronic kidney diseases.

Urine sediment examination or dipstick for red blood cells and white blood cells should be performed in patients with chronic kidney disease and in individuals at increased risk of developing chronic kidney disease.

Imaging studies of the kidneys should be performed in patients with chronic kidney disease and in selected individuals at increased risk of developing chronic kidney disease.

Although several novel urinary markers (such as tubular or low-molecular weight proteins and specific mononuclear cells) show promise of future utility, they should not be used for clinical decision-making at present.

ASSOCIATION OF LEVEL OF GFR WITH COMPLICATIONS IN ADULTS (PART 6, p. S111)

Many of the complications of chronic kidney disease can be prevented or delayed by early detection and treatment. The goal of Part 6 is to review the association of the level of GFR with complications of chronic kidney disease to determine the stage of chronic kidney disease when complications appear. As described in Appendix 1, Table 152, the Work Group searched for crosssectional studies that related manifestations of complications and the level of kidney function. Data from NHANES III were also analyzed, as described in Appendix 2.

Estimated prevalence of selected complications, by category of estimated GFR, among participants age 20 years in NHANES III, 1988 through 1994. These estimates are not adjusted for age, the mean of which is 33 years higher at an estimated GFR of 15 to 29 mL/min/1.73 m2 than that at an estimated GFR 90 mL/min/1.73 m2.

Estimated distribution of the number of complications shown in figure by category of estimated GFR among participants age 20 years in NHANES III, 1988 through 1994. These estimates are not adjusted for age, the mean of which is 33 years higher at an estimated GFR of 15 to 29 mL/min/1.73 m2 than that at an estimated GFR of 90 mL/min/1.73 m2.

Because of different manifestations of complications of chronic kidney disease in children, especially in growth and development, the Work Group limited the scope of the review of evidence to adults. A separate Work Group will need to address this issue in children.

The Work Group did not attempt to review the evidence on the evaluation and management of complications of chronic kidney disease. This is the subject of past and forthcoming clinical practice guidelines by the National Kidney Foundation and other groups, which are referenced in the text.

Representative findings are shown by stage of chronic kidney disease in the figures above and below, showing a higher prevalence of each complication at lower GFR, and a larger mean number of complications per person and higher prevalence of multiple complications at lower GFR. These and other findings support the classification of stages of chronic kidney disease and are discussed in detail in Guidelines 7 through.

Guideline 7.
Association of Level of GFR With Hypertension (p. S112)

High blood pressure is both a cause and a complication of chronic kidney disease. As a complication, high blood pressure may develop early during the course of chronic kidney disease and is associated with adverse outcomes—in particular, faster loss of kidney function and development of cardiovascular disease.

Blood pressure should be closely monitored in all patients with chronic kidney disease.

Treatment of high blood pressure in chronic kidney disease should include specification of target blood pressure levels, nonpharmacologic therapy, and specific antihypertensive agents for the prevention of progression of kidney disease (Guideline 13) and development of cardiovascular disease (Guideline 15).

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification

Archives Medical Review Journal. 2013; 22(2): 221-229

Akut böbrek hasarı glomerüler filtrasyon hızında, hızlı azalma ile beraber üre ve kreatinin gibi nitrojen artık ürünlerinin birikimi, sıvı ve elektrolit, asit ve baz dengesinin bozulması ile kendini gösteren klinik bir sendromdur. Özelikle birkaç komorbid hastalığı olan kişilerde sık görülen ve mortaliteyi artıran önemli bir klinik problemdir. Hastanede yatan hastaların %5’inde, yoğun bakım hastalarının ise %30-50’sinde görülebilmektedir. Halen kullandığımız seri kreatinin ölçümü ve idrar miktarı böbrek hasarının erken tanınmasına olanak vermemektedir. Serum kreatinin düzeyi yaşa, kiloya, hastanın hidrasyon durumuna göre değişkenlik göstermekte ve böbrek hasarı %50 gibi yüksek bir orana ulaşmadıkça artmayabilmektedir. Bu nedenle yeni belirteçlere ihtiyaç duyulmuştur. Bu derlemede, üzerinde en fazla çalışılan belirteçler, nötrofil jelatinaz ilişkili lipokalin, sistain-C, kidney injury molekül-1, liver fatty acid binding proteinler ve IL-18’i gözden geçireceğiz

Blood Purif. 2010;29(4):357-65

Abstract
Acute kidney injury (AKI) is a frequent clinical problem in critically ill patients and the associated mortality is high. Standard serum and urine biomarkers are insensitive and nonspecific for the detection of kidney injury in its early stages which limits the therapeutic options and may compromise the outcome. The study presents new candidates for biochemical markers of AKI, with potentially high sensitivity and specificity, causally related to its pathogenesis and development. Some of these biomarkers measured in serum or urine are well known in laboratory practice but have been used in other tests, while some novel biomarkers have been proposed as a result of experimental and clinical studies. In current clinical practice, identification and classification of AKI is based on elevations in serial serum creatinine concentrations, which are delayed and therefore unreliable in the acute setting. The most promising of the new serum AKI markers are cystatin C, neutrophil gelatinase-associated lipocalin and uric acid. Urinary AKI markers may be classified as enzymes released from damaged tubular cells (alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminopeptidase, isoenzymes of glutathione transferase, N-acetyl-beta-D-glucosaminidase), low-molecular-weight proteins (alpha(1)-microglobulin, beta(2)-microglobulin, retinol-binding protein, cystatin C) and proteins specifically produced in the kidney and associated with the development of AKI [cysteine-rich protein 61, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, cytokines and chemokines (Gro-alpha, IL-18), and structural and functional proteins of renal tubules (F-actin, Na(+)/H(+) exchange isoform 3)]. Based on the different expression of these markers, using a panel of serum and urine markers may potentially help to distinguish between various types of insults, establish the duration and severity of injury, predict the clinical outcome and help to monitor response to treatment in AKI.

Circ J. 2010;74(7):1274-82.

Abstract
Chronic kidney disease (CKD) is frequently associated with a progressive decrease in the glomerular filtration rate, which leads to endstage renal disease (ESRD). Heart failure (HF) is a complex syndrome rather than a primary diagnosis, and considered as the endpoint of all cardiovascular disorders. It is the leading cause of death among the cardiovascular diseases in patients with CKD and ESRD. There is some interaction between the heart and kidney (the so-called “cardiorenal syndrome”), and HF patients with the complication of CKD or ESRD show a worse prognosis. Thus, early diagnosis and aggressive management of HF are needed in patients with CKD and ESRD. A number of biomarkers appear to have growing clinical importance and are reported for detection and stratification of HF. Although HF and CKD have a close interrelationship, the utility of the biomarkers has not been adequately studied with regard to the relationship with renal dysfunction. This paper reviews of the current evidence about laboratory biomarkers in patients with HF or CKD, emphasizing the emerging cardiac biomarkers (ie, BNPs and cardiac troponins), and the biomarkers of renal injury (ie, cystatin C and neutrophil gelatinase-associated lipocalin). Furthermore, it discusses the potential role of these markers in terms of heart – kidney interactions and their utility in the diagnostic and therapeutic strategies for cardiorenal syndrome.