Competencias adquiridas académicamente

Demographic Data

The age of the patients ranged between 18 and 56 years (median; 25 years) with a female preponderance (57.1%) (Fig1-2). Duration of management for SCD ranged between 6 and 46 years (mean ± SD; 22.3± 8.0). The Hb genotype was SS in 57 (81.4%) and SC in 13 (18.6%) patients(Fig 3). The mean ages for HbSS and HbSC were 26.3(+8.3) years and 32.92(+9.34) years respectively (p=0.01) (Table 1).

FIGURE 7: AGE DISTRIBUTION OF SCD PATIENTS

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FIGURE 8: SEX DISTRIBUTION OF STUDIED SCD PATIENTS

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FIGURE 9: HAEMOGLOBIN GENOTYPE OF PATIENTS

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Table 1: COMPARISON OF ANTHROPOMETRIC AND CLINICAL PARAMETERS BETWEEN MALES (N=30) AND FEMALES (N=40)

VARIABLE MEAN±SD P VALUE

Age (Years) Male Female All

27.0±9.0 27.9±8.9 27.5±8.9

P=0.690

Vaso-occlusive crisis/yr Male

Female All

2.2±1.2 2.3±1.2 2.3±1.2

P=0.583

Body Mass index (kg/m²)

Male Female All

18.2±3.0 20.4±5.0 19.5±4.4

P=0.05

Weight (kg)

Male Female All

51.2±12.0 51.8±12.0 51.5±12.0

P=1.000

Systolic BP (mmHg)

Male Female All

110±14.3 105±11.0 107±12.6

P=0.272

Diastolic BP (mmHg)

Male Female All

67.0±10.6 65.3±9.6 66.0±10.0

P=0.556

MABP (mmHg)

Male Female All

81.2±10.7 78.7±9.2 79.8±9.9

P=0.344

56 Vaso-occlusive crisis (VOC)

Mean(±SD) number of crises of 2.27(+1.17) per year was observed in all the patients while that for HbSS and HbSC were 2.49(±1.17) and 1.31(±0.48) per year respectively (p<0.0001). The number of crises per year negatively correlated with body mass index (r=-0.413; p<0.0001), GFR (-0.523; p<0.0001) and haemoglobin (-0.338;

p=0.004).

History of Renal Disease

The symptoms and signs of renal disease reported by the subjects were haematuria (40%), nocturia (38.6%), frothy urine (31.4%) and recurrent body swelling (17.1%).

Anthropometric and Clinical Parameters

The mean body mass index for all patients was 19.45(+4.35)kg/m², while that for HbSS and HbSC patients were 18.17(+2.65)kg/m² and 25.1(+5.84)kg/m² respectively (p<0.0001). The mean SBP for males and females were 110(±14.3)mmHg and 105(±11.0)mmHg respectively (p=0.272) while their mean DBP were 67(±10.6)mmHg and 65.3(±9.3)mmHg respectively (p=0.556)(Table 1). The patients with HbSS and HbSC had SBP of 107 (±11.9)mmHg and 108(±15.8)mmHg respectively (p=0.809) while their DBP were 66.1(±10.1)mmHg and 65.4(±9.7)mmHg respectively (p=0.832)(Table 2). There was positive correlation between GFR and BMI (r=0.518, p<0.0001) (Fig 4).

Table 2: COMPARISON OF ANTHROPOMETRIC AND CLINICAL PARAMETERS BETWEEN HBSS (N=57) AND HBSC (N=13) PATIENTS

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VARIABLE MEAN±SD P VALUE

Age (Years) Hb-SS Hb-SC

26.3+8.4 32.9+9.3

P=0.01 Vaso-occlusive crisis/yr

Hb-SS Hb-SC

2.5±1.2 1.3±0.5

P=0.001

Body Mass index (kg/m²)

Hb-SS

Hb-SC 18.2±2.6

25.1±5.8

P<0.0001 Weight(kg)

Hb-SS Hb-SC

48.8±10.0 63.5±13.0

P<0.0001 Systolic BP (mmHg)

Hb-SS Hb-SC

107±11.9 108±15.8

P=0.809 Diastolic BP (mmHg)

Hb-SS Hb-SC

66.1±10.1 65.4±9.7

P=0.832 MABP (mmHg)

Hb-SS Hb-SC

79.8±9.8 79.4±10.7

P=0.825

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FIGURE 10: RELATIONSHIP BETWEEN GLOMERULAR FILTRATION RATE AND BODY MASS INDEX (r = 0.518, p < 0.0001)

Markers of Kidney Damage

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Thirty-two (45.7%) had microalbuminuria, proteinuria or reduced GFR<60ml/min or in different combinations while the remaining thirty-eight (54.3%) patients had no evidence of kidney dysfunction. If patients with isolated microalbuminuria were excluded, the combination of patients with proteinuria, GFR

<60ml/min and microalbuminuria will add up to 25 which is 35.7% of the studied population. Twelve (17.1%) patients had microalbuminuria, 4 (5.7%) had overt proteinuria while 54 (77.2%) patients had no proteinuria (Fig 5).

FIGURE 11: PATTERN OF PROTEINURIA OF STUDIED SCD PATIENTS

Twenty-four-hour protein excretion ranged from 0.56 to 1.70g per day with a mean (±SD) of 1.2± (0.6g)/24hrs. Pattern of kidney damage is as shown in Table 3.

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Table 3: PATTERN OF KIDNEY DAMAGE IN STUDIED PATIENTS

Microalbuminuria – ACR of 30mg/g to ≤299mg/g.

Overt Proteinuria – Protein excretion >300mg/24hrs.

Five (7.1%) patients had hyperfiltration (GFR >120ml/min), 23 (32.9%) had GFR<60ml/min, 7 (10%) had isolated microalbuminuria, 2 (2.9%) had isolated overt proteinuria, 16 (22.9%) had isolated GFR <60ml/min, 5 (7.1%) had combination of

MARKERS OF KIDNEY DAMAGE FREQUENCY PERCENTAGES

Hyperfiltration 5 7.1

Microalbuminuria 7 10

Overt Proteinuria 2 2.9

GFR<60ml/min 16 22.9

Microalbuminuria +GFR<60ml/min 5 7.1 Proteinuria + GFR<60ml/min 2 2.9 Proteinuria +GFR<60ml/min +Microalbuminuria 25 35.7

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microalbuminuria and reduced GFR while 2 (2.9) had both overt proteinuria and reduced GFR (Table 4).

Table 4: PATTERN OF KIDNEY FUNCTION IN STUDIED PATIENTS

KIDNEY FUNCTION FREQUENCY PERCENTAGE (%) By Proteinuria

Microalbuminuria Overt Proteinuria No Proteinuria

12 4 54

17.1 5.7 77.2 By GFR

Hyperfiltration (>120ml/min) Reduced GFR(<60ml/min) Normal (90-120ml/min)

5 23 42

7.1 32.9 60

Table 5 shows stratification of patients according to NKF/KDOQI recommended staging of chronic kidney disease(CKD).

Table 5: PATTERN OF CKD ACCORDING TO NKF/KDOQI CKD STAGING

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The mean age of patients with CKD was 27.2(±9.4)years and was not statistically significant when compared with those without CKD(p=0.623, Mann-Whitney test) (Table 6).

STAGE DESCRIPTION FREQUENCY PERCENTAGE (%)

1 GFR ≥90ml/min+Proteinuria 2 2.9

2 GFR 60-89ml/min OR Proteinuria

23 32.9

3 GFR 30-59ml/min 23 32.9

4

GFR 15-29ml/min 0 0

5 GFR<15ml/min 0 0

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Table 6: COMPARISON OF ANTHROPOMETRIC AND CLINICAL PARAMETERS BETWEEN CKD (N=25) AND NON-CKD (N=45) PATIENTS

VARIABLE MEAN±SD P VALUE

Age(Years) NO CKD CKD

27.2+9.4 27.7+8.6

P=0.623 Vaso-occlusive crisis/yr

NO CKD CKD

1.8±1.0 3.3±0.8

P<0.0001 Number of transfusion/yr

NO CKD CKD

3.6±4.9 3.5±2.2

P=0.09

Body Mass index (kg/m²) NO CKD

CKD 20.7±4.5

16.8±2.4

P<0.0001 Weight (kg)

NO CKD CKD

56.2±10.8 41.3±7.1

P<0.0001 Systolic BP (mmHg)

NO CKD CKD

109±13.5 104±9.5

P=0.148 Diastolic BP (mmHg)

NO CKD CKD

66.9±10.6 64.1±8.5

P=0.346 MABP (mmHg)

NO CKD CKD

80.9±10.7 77.3±7.5

P=0.211

There was a relationship between the haemoglobin genotype and propensity for kidney disease(p<0.0001). Of the 57 patients with HbSS, 24(42.1%) had evidence of kidney disease compared with 1(7.7%) of the 13 patients with HbSC (p<0.0001);(Table 7).

Therefore, CKD was more common among HbSS than HbSC subjects.

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Table 7: RELATIONSHIP BETWEEN HAEMOGLOBIN GENOTYPE AND PROPENSITY FOR KIDNEY DISEASE

HAEMOGLOBIN GENOTYPE

SCD WITH CKD SCD WITHOUT CKD

P VALUE

Hb-SS 24 33

Fischer’s exact test, P<0.0001

Hb-SC 1 12 TOTAL 25 45

No statistically significant difference was observed in the sex distribution (Table 8).

Table 8: RELATIONSHIP BETWEEN GENDER AND PROPENSITY FOR KIDNEY DISEASE IN STUDIED PATIENTS

GENDER SCD WITH CKD SCD WITHOUT CKD

P VALUE

MALE 8 22 P=0.118

χ² =1.429

FEMALE 17 23

TOTAL 25 45

Serum biochemical parameters is as shown in Table 9; no significant difference was observed in the gender and haemoglobin genotype of the studied patients. The GFR negatively correlated with microalbuminuria (Fig 6).

Table 9: BIOCHEMICAL PARAMETERS OF STUDIED PATIENTS (N=70)

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PARAMETERS MEAN VALUE ±SD REFERENCE RANGE Creatinine (µmol/L) 87.9±17.5 90-132

Urea (mmol/L) 3.8±1.3 3-6

Sodium (mmol/L) 137±1.9 135-148

Potassium (mmol/L) 4.3±0.4 3.5-5.5

Bicarbonate (mmol/L) 24.0±2.0 22-28

Chloride (mmol/L) 102.2±3.2 96-112

Anion Gap 10.8±3.3 10-14

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FIGURE 12: RELATIONSHIP BETWEEN GLOMERULAR FILTRATION RATE (GFR) AND MICROALBUMINURIA (r = - 0.255, p = 0.04)

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The pattern of tubular function in SCD patients is as shown in Table 10. Mean (±SD) of fractional excretion of sodium (FENa), fractional excretion of potassium (FEK), specific gravity and pH were 6.5 (±2.2), 31.1 (±10.1), 1.0 (±0.004) and 6.3 (±0.5) respectively.

Table 10: PATTERN OF TUBULAR DYSFUNCTION AMONG SCD PATIENTS

GFR positively correlated with specific gravity(r=0.644, p<0.0001) while it negatively correlated with FENa and FEK respectively (Fig 7-8). Also, percentage sickled cell count inversely correlated with specific gravity(r=-0.532; p<0.0001). There was no correlation between age of subjects and FENa (r=0.002; p=0.987), FEK (r=0.176; p=0.146) as well as specific gravity (-0.153; p=0.205).

PARAMETER (N=70)

RANGE REFERENCE

RANGE

ABNORMAL (Cut Off )

FREQUENCY (%)

FEK 13.2-55.9 8-10% >10% 70 (100%)

FENa 2.7-11.8 1-3% >3% 69 (98.6%)

Specific gravity 1.000-1.015 1.010-1.020 <1.010 60 (85.7%)

PH 5.5-7.5 4.6-8.0 >6.5 46 (65.7%)

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FIGURE 13: RELATIONSHIP BETWEEN GLOMERULAR FILTRATION RATE (GFR) AND FRACTIONAL EXCRETION OF POTASSIUM (r = -0.448, p<0.0001)

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Figure 14 : RELATIONSHIP BETWEEN GLOMERULAR FILTRATION RATE (GFR) AND FRACTIONAL EXCRETION OF SODIUM (r = - 0.336; p = 0.004)

70 Haematological Parameters

Mean values for haematocrit, white blood cell count (WBC) and platelet count were 24.7 (±5.4)%, 9.8 (±93.6) χ 10³/µL and 300 (±140) χ 10³/mm³ respectively while red blood cell count (RBC), reticulocyte index and percentage sickle cell count were 1.0 (±0.9) x 10⁶/ µL, 0.6 (±0.7)% and3.5 (±3.1)% respectively. Mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) were 82.4 (±9.4)fL, 26.8 (±3.4)pg and 32.5 (±1.5)% respectively (Table 11).

Table 11: HAEMATOLOGICAL PARAMETERS OF SUBJECTS (N=70)

PARAMETERS MEAN VALUE±SD REFERENCE RANGE

Haemoglobin (g/dL) 8.0±1.9 14-18

Haematocrit(%) 24.7±5.4 34-48

WBC(µL) 9.8±3.6 χ 10³ 4-11 χ10³

RBC(µL) 1±0.9 χ 10⁶ 3.8-5.6 χ 10⁶

MCV(fL) 82.4±9.4 78-98

MCH(pg) 26.8±3.4 27-35

MCHC (%) 32.5±1.5 31-37

Platelet count(µL) 300±140 χ 10³ 150-450 χ 10³ Percentage sickle cell count (%) 3.5±3.1 <3%

Reticulocyte index (%) 0.6±0.7 >2%

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Haematocrit and RBC were significantly lower among Hb-SS cohorts compared to Hb-SC (p<0.0001) while percentage sickle cell count, reticulocyte index, WBC and MCV were significantly higher among Hb-SS compared to Hb-SC (p<0.0001).

The difference in haematological profile between CKD patients and those without CKD is as shown in Table 12. Haematocrit, reticulocyte index and RBC were significantly lower among CKD groups compared to those without CKD (p<0.05) while percentage sickle cell count and MCV were significantly higher among CKD group (p<0.05).

Table 12: COMPARISON OF HAEMATOLOGICAL PARAMETERS BETWEEN CKD (N=25) AND NON-CKD (N=45) PATIENTS

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PARAMETER MEAN±SD P VALUE

Haemoglobin (g/dL) NO CKD CKD

8.4±1.9 7.3±1.6

P=0.03 Haematocrit (%)

NO CKD CKD

25.7±5.3 22.4±5.1

P=0.03 WBC (µL)

NO CKD CKD

10.0±3.9х10³ 9.2±2.5 х10³

P=0.631 RBC (µL)

NO CKD CKD

3.3±0.9х10⁶ 2.7±0.8х10⁶

P=0.02 MCV(fL)

NO CKD CKD

80.6±9.0 86.4±9.0

P=0.02 MCH(pg)

NO CKD CKD

26.3±3.4 27.9±3.4

P=0.07 MCHC (%)

NO CKD CKD

32.5±1.4 32.3±1.7

P=0.839 Platelet (µL)

NO CKD CKD

371±104 х10³ 348±179 х10³

P=0.186

Percentage sickle cell count (%) NO CKD

CKD

2.1±2.5 6.4±1.9

P<0.0001 Reticulocyte index (%)

NO CKD CKD

0.8±0.9 0.5±0.6

P=0.02

GFR correlated positively with haemoglobin (r=0.472, p<0.0001) (Fig 9) and while it however correlated negatively with percentage sickle cell count(r=-0.616,

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p<0.0001) (Fig 10) and number of painful crisis (r = - 0.523; p<0.0001). Also, microalbuminuria correlated positively with percentage sickle cell count(r=0.326, p=0.008) (Fig 11).

FIGURE 15 : RELATIONSHIP BETWEEN GLOMERULAR FILTRATION RATE AND HAEMOGLOBIN (r = 0.472; p <0.0001)

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FIGURE 16: RELATIONSHIP BETWEEN PERCENTAGE SICKLE CELL COUNT AND GLOMERULAR FILTRATION RATE (r = - 0.616; p < 0.0001)

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FIGURE 17: RELATIONSHIP BETWEEN MICROALBUMINURIA AND PERCENTAGE SICKLE CELL COUNT (r = 0.326; p=0.008)

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In addition, percentage sickled cell count also significantly correlated with FEK

which is a marker of tubular dysfunction(r=0.308, p=0.01) (Fig 12). Haemoglobin correlated negatively with reticulocyte index (r=-0.666, p<0.0001) (Fig 13).

FIGURE 18: RELATIONSHIP BETWEEN FRACTIONAL EXCRETION OF POTASSIUM AND PERCENTAGE SICKLE CELL COUNT (r = 0.308; p = 0.01)

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FIGURE 19: RELATIONSHIP BETWEEN RETICULOCYTE INDEX AND HAEMOGLOBIN (r = 0.666;

p<0.0001)

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On subjecting the data to logistic regression analysis to determine which of the measured parameters actually predicts development of chronic kidney disease;

percentage sickled cell count was still significant in predicting chronic kidney disease with odd ratio (confidence interval) of 0.49 (0.26-0.92) (Table 13).

TABLE 13: RESULTS OF MULTIPLE REGRESSION ANALYSIS SHOWING REGRESSION COEFFICIENTS, 95% CONFIDENCE INTERVAL AND P-VALUE.

Measured Variables Regression coefficient

Standard error

Odd ratio (95% CI)

P-value

Age 0.021 0.069 1.02(0.89-1.17) 0.763

BMI -0.319 0.229 1.38(0.89-2.16) 0.164

Microalbuminuria 0.139 1.322 1.15(0.09-15.3) 0.916 Haemoglobin -0.084 0.397 0.92(0.42-2.00) 0.832

% sickled count count 0.717 0.322 0.49(0.26-0.92) 0.03

FEK 0.005 0.101 1.01(0.83-1.23) 0.961

FENa 0.347 0.467 1.42(0.57-3.54) 0.457

Analysis of Renal-Biopsy Specimen

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Of the 25 patients with CKD, 23 underwent renal biopsy out of which 1 report was inconclusive. The remaining 2 patients declined renal biopsy.

Glomerular lesions:

Glomerulosclerosis was demonstrated in 9 (39.1%) of the patients. The biopsy specimen showed perihilar focal and segmental glomerulosclerosis and this was sometimes accompanied by global sclerosis. The sclerotic segments were typically adherent to Bowman’s capsule and sometimes contained foci of hyalinosis. 6(69.6%) had matrix expansion while 15 (65.2%) had mesangial hypercellularity. No glomerular basement membrane thickening or duplication was seen in any of the patients (Table 14).

Tubular/interstitial lesions:

Tubular thickening was found in 7(30.4%) patients while tubular atrophy was demonstrated in 14(60.9%) of the patients. Interstitial fibrosis was demonstrated in 14(60.9) patients while interstitial cellular infiltration with inflammatory cells was demonstrated in nine 2(8.7%) of the patients. However, no papillary necrosis was seen. The focus of tubulointerstitial injury could often be identified adjacent to glomeruli with segmental or global sclerosis.

Vascular lesions:

Medial arteriolar thickening was seen in 4 (17.4%) patients while intimal fibrosis was found in 7 (30.4)% of the patients.

Histological Diagnosis:

80

Pattern of histological diagnosis is as shown in Table 18. Eleven (50%) had mesangioproliferative glomerulonephritis, 6 (27.3%) had minimal change disease, 3 (13.6%) had focal segmental glomerulosclerosis and 2 (9.1%) had interstitial nephritis (Fig 14-18).

Table 14: Histological findings in biopsied CKD patients

LESION PRESENT (%) ABSENT (%)

Glomerular sclerosis 9(39.1) 14(60.9)

Mesangial expansion 16(69.6) 7(30.4)

Mesangial hypercellularity 15(65.2) 8(34.8)

Tubular thickening 7(30.4) 16(69.6)

Tubular atrophy 14(60.9) 9(39.1)

Interstitial fibrosis 14(60.9) 9(39.1)

Interstitial cell infiltrates 2(8.7) 21(91.3)

Medial thickening 4(17.4) 19(82.6)

Intimal fibrosis 7(30.4) 16(69.6)

Myointimal hyalinosis 5(21.7) 18(78.3)

Table 15: HISTOLOGICAL PATTERN IN CKD PATIENTS AS SEEN BY LIGHT MICROSCOPY

Histological Findings (N=22) Frequency Percentage (%)

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Mesangioproliferative GN 11 50 Minimal change disease 6 27.3 Focal segmental glomeruloslcerosis 3 13.6 Interstitial nephritis 2 9.1

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Figure 14: Kidney histology showing minimal change disease. Magnification, X100 (H&E).

A normal glomerulus showing normal capillary loops vascular pole and urinary pole. No

mesangial hypercellularity or increased mesangial matrix. No glomerular basement

membrane thickening.

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Figure 15: Kidney histology showing mesangial proliferation and increased mesangial matrix.

Magnification, X100 (H&E).

Mesangial hypercellularity with increased mesangial matrix. No GBM thickening or

duplication. No inflammatory cells within the capillary loops.

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Figure 16: Kidney histology showing global sclerosis. Magnification X100 (H&E).

Globally sclerotic glomerulus. There is increased extracellular matrix and hyalinosis.

There is adhesion to Bowman’s capsule. There is infiltration of the interstitium by inflammatory cells.

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Figure 17: Kidney histology showing global sclerosis with interstitial fibrosis and tubular atrophy (IFTA). Magnification, X100 (H&E).

Cortical interstitial fibrosis with tubular atrophy. Some of the tubules show features of

acute tubular necrosis with simplification of the epithelium.

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Figure 18: Kidney histology showing interstitial nephritis. Magnification, X100 (H&E)

There are dense interstitial infiltrates.

87 CHAPTER FIVE

In document Identificación de competencias profesionales de psicólogos requeridas para su inserción laboral en los ámbitos clínico empresarial y educativo 2011, Quito (página 36-42)